chr11-66211206-C-T
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PP3PP5_Very_Strong
The NM_018026.4(PACS1):c.607C>T(p.Arg203Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PACS1
NM_018026.4 missense
NM_018026.4 missense
Scores
10
7
2
Clinical Significance
Conservation
PhyloP100: 2.35
Genes affected
PACS1 (HGNC:30032): (phosphofurin acidic cluster sorting protein 1) This gene encodes a protein with a putative role in the localization of trans-Golgi network (TGN) membrane proteins. Mouse and rat homologs have been identified and studies of the homologous rat protein indicate a role in directing TGN localization of furin by binding to the protease's phosphorylated cytosolic domain. In addition, the human protein plays a role in HIV-1 Nef-mediated downregulation of cell surface MHC-I molecules to the TGN, thereby enabling HIV-1 to escape immune surveillance. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.792
PP5
Variant 11-66211206-C-T is Pathogenic according to our data. Variant chr11-66211206-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 39581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-66211206-C-T is described in Lovd as [Pathogenic]. Variant chr11-66211206-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PACS1 | NM_018026.4 | c.607C>T | p.Arg203Trp | missense_variant | Exon 4 of 24 | ENST00000320580.9 | NP_060496.2 | |
| PACS1 | XM_011545162.2 | c.313C>T | p.Arg105Trp | missense_variant | Exon 4 of 24 | XP_011543464.2 | ||
| PACS1 | XM_011545164.3 | c.268C>T | p.Arg90Trp | missense_variant | Exon 4 of 24 | XP_011543466.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PACS1 | ENST00000320580.9 | c.607C>T | p.Arg203Trp | missense_variant | Exon 4 of 24 | 1 | NM_018026.4 | ENSP00000316454.4 | ||
| PACS1 | ENST00000527380.1 | c.313C>T | p.Arg105Trp | missense_variant | Exon 4 of 5 | 4 | ENSP00000432639.1 | |||
| PACS1 | ENST00000533756.5 | c.298C>T | p.Arg100Trp | missense_variant | Exon 5 of 5 | 4 | ENSP00000437150.1 | |||
| PACS1 | ENST00000527224.1 | n.731C>T | non_coding_transcript_exon_variant | Exon 4 of 7 | 2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461438Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727020
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:52
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Schuurs-Hoeijmakers syndrome Pathogenic:35
| Pathogenic, criteria provided, single submitter | research | Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital | Oct 04, 2024 | PS2,PS4,PM2,PP3 - |
| Pathogenic, criteria provided, single submitter | clinical testing | Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India | - | - - |
| Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 07, 2012 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | DASA | Jun 10, 2022 | The c.607C>T;p.(Arg203Trp) missense change has been observed in affected individual(s) and ClinVar contains an entry for this variant (Clinvar ID: 39581; PMID: 23159249; 25522177; 26795593; 26842493; 28111752; 30588754) - PS4.Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 23159249) - PS3_supporting. The variant is present at low allele frequencies population databases (rs398123009– gnomAD 0.00006572%; ABraOM no frequency - http://abraom.ib.usp.br/) -PM2_supporting. The variant was assumed de novo, but without confirmation of paternity and maternity (PMID: 23159249; 25522177; 33166031) PM6_strong. In summary, the currently available evidence indicates that the variant is Pathogenic - |
| Pathogenic, criteria provided, single submitter | research | HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology | Apr 13, 2017 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2016 | This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PS3,PM1,PM2,PP2,PP3. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Eurofins-Biomnis | Oct 20, 2022 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre | Dec 19, 2024 | - - |
| Pathogenic, no assertion criteria provided | clinical testing | Service de Génétique Moléculaire, Hôpital Robert Debré | Jul 17, 2020 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Wangler Lab, Baylor College of Medicine | - | This missense PACS1 variant at c.607C>T (p.R203W) variant in the PACS1 was seen on exome through the Texome project (R01HG011795) as a de novo variant in the patient (PS2). This recurrent de novo variant has been previously reported in more than 20 individuals with Schuurs-Hoeijmakers syndrome (PMID: 26842493, 30588754). This variant has not been observed in gnomAD (PM2). Functional studies demonstrated that this variant forms cytoplasmic aggregates with increased protein stability, consistent with a dominant-negative mechanism (PMID: 23159249) (PS3). This variant has a deleterious prediction score (CADD: 29.4) (PP3), and the evolutionary conservation of this residue is high. We classify this variant as pathogenic. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Victorian Clinical Genetics Services, Murdoch Childrens Research Institute | Oct 09, 2024 | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0104 - Dominant negative is a known mechanism of disease in this gene and is associated with Schuurs-Hoeijmakers syndrome (MIM#615009). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to tryptophan. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (1 heterozygote, 0 homozygotes). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. p.(Arg203Gln) has been observed as a de novo variant in a patient with Schuurs-Hoeijmakers syndrome (PMID: 28975623). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported to be de novo in more than twenty individuals with Schuurs-Hoeijmakers syndrome (ClinVar, PMID: 23159249, 25522177, 26842493). (SP) 1002 - This variant has moderate functional evidence supporting abnormal protein function. In vitro assays demonstrated formation of cytoplasmic aggregates, leading to protein-trafficking defects (PMID: 23159249). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign - |
| Pathogenic, criteria provided, single submitter | clinical testing | Centogene AG - the Rare Disease Company | May 11, 2021 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego | Aug 04, 2020 | This variant has been previously reported as a recurrent de novo change in patients with seizures, dysmorphic features, gastroesophageal reflux, cardiac abnormalities, intellectual disability, speech delay, (PMID: 28111752, 26842493). In vivo studies of the p.Arg203Trp variant in zebrafish embryos observed that it induces craniofacial defects, most likely in a dominant-negative fashion. This phenotype is driven by aberrant specification and migration of SOX10-positive cranial, but not enteric, neural-crest cells (PMID: 23159249). It is absent from the gnomAD population database and thus is presumed to be rare. The c.607C>T (p.Arg203Trp) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.607C>T (p.Arg203Trp) variant is classified as Pathogenic. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | Jun 05, 2018 | - - |
| Likely pathogenic, no assertion criteria provided | literature only | ClinVar Staff, National Center for Biotechnology Information (NCBI) | Jun 27, 2013 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille | - | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Jul 28, 2017 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 20, 2016 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Jan 16, 2024 | Criteria applied: PS2_VSTR,PS4,PM2_SUP,PP2 - |
| Pathogenic, criteria provided, single submitter | clinical testing | Génétique des Maladies du Développement, Hospices Civils de Lyon | Mar 10, 2017 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Daryl Scott Lab, Baylor College of Medicine | Nov 10, 2023 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 30, 2023 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | New York Genome Center | May 27, 2020 | The de novo p.Arg203Trp variant identified in PACS1 is a known pathogenic recurrent de novo variant that has been reported in multiple affected individuals in the literature [PMID: 26842493; PMID: 23159249; PMID: 25522177]. The variant has been reported in the ClinVar database by multiple laboratories and is classified as pathogenic (ClinVar Variation ID: 39581). The p.Arg203Trp variant has 0.000007 allele frequency in the gnomAD(V3) database (1 out of 143,260 heterozygous alleles) indicating it is not a common benign variant in the populations represented in that database. The variant affects a highly conserved residue and is predicted deleterious by multiple in silico prediction tools. In vitro functional studies have shown that the p.Arg203Trp variant forms cytoplasmic aggregates resulting in defective protein trafficking, suggestive of a dominant-negative mechanism of disease [PMID: 23159249]. Based on the available evidence, the p.Arg203Trp variant in the PACS1 gene is assessed as Pathogenic. - |
| Pathogenic, no assertion criteria provided | clinical testing | Pediatric Genetics Clinic, Sheba Medical Center | May 13, 2021 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | Nov 23, 2015 | - - |
| Pathogenic, criteria provided, single submitter | research | Department of Paediatrics and Adolescent Medicine, The University of Hong Kong | Jun 02, 2020 | - - |
| Pathogenic, no assertion criteria provided | clinical testing | Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) | Apr 01, 2023 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 13, 2022 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München | Feb 23, 2023 | - - |
| Pathogenic, no assertion criteria provided | provider interpretation | GenomeConnect - Simons Searchlight | Jan 14, 2019 | Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2019-01-14 and interpreted as Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight. - |
| Pathogenic, criteria provided, single submitter | clinical testing | Breda Genetics srl | Jul 29, 2020 | The variant c.607C>T (p.Arg203Trp) in PACS1 is reported as pathogenic for Schuurs-Hoeijmakers syndrome in ClinVar (Variation ID: 39581) and as affects function in the Global Variome shared LOVD database v.3.0. There is no information on frequency in gnomAD, 1000 Genomes or NHLI Exome Sequencing Project (ESP). The nucleotide position is conserved across 35 mammalian species (GERP RS: 4.79). In silico analysis indicates that the variant might be damaging. This mutation has been firstly reported by Schuurs-Hoeijmakers et al. (2012) in 2 unrelated boys with mental retardation and a strikingly similar facial appearance. Later, different other groups reported the same de novo recurrent pathogenic variant in patients with a similar phenotype (Gadzicki et al., 2015; Martinez-Monseny et al.,2018; Dutta et al., 2019 and many others). - |
| Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 18, 2017 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | 3billion, Medical Genetics | Oct 02, 2021 | Same nucleotide change resulting in same amino acid change has been previously reported at least twice as de novoo in similarly affected indivisual (PMID: 25533962, 23159249, PS2, PS4_M). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). It is not observed in the gnomAD v2.1.1 dataset (PM2). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. - |
| Pathogenic, no assertion criteria provided | research | Laboratory of Medical Genetics, University of Torino | Mar 14, 2021 | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 29, 2024 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 203 of the PACS1 protein (p.Arg203Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with intellectual disability and/or epilepsy (PMID: 26795593, 26842493). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 39581). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PACS1 protein function. Experimental studies have shown that this missense change affects PACS1 function (PMID: 23159249). For these reasons, this variant has been classified as Pathogenic. - |
not provided Pathogenic:9
| Pathogenic, criteria provided, single submitter | clinical testing | Laboratoire de Génétique Moléculaire, CHU Bordeaux | - | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2021 | - - |
| Pathogenic, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | Clinical Genetics and Genomics, Karolinska University Hospital | Nov 11, 2016 | - - |
| Pathogenic, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
| Pathogenic, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
| Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 15, 2022 | Published functional studies indicate that the R203W variant perturbs normal PACS1 function by forming cytoplasmic aggregates, resulting in altered protein-trafficking, possibly suggesting a dominant-negative effect on the protein (Schuurs-Hoeijmakers et al., 2012); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25533962, 28135719, 25356970, 27959697, 26842493, 29656858, 23159249, 26795593, 26944241, 28111752, 28554332, 28628100, 28867141, 27875746, 30690871, 30588754, 30113927, 31330568, 25522177, 28975623, 28471432, 31988453, 30577886, 32963807, 33166031, 33333793, 30755392, 33144682, 32903913, 33726816, 34068396, 31785789) - |
| Likely pathogenic, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Feb 08, 2023 | PS4, PM2_SUP, PP2 - |
| Pathogenic, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jul 07, 2016 | - - |
Global developmental delay Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Génétique des Maladies du Développement, Hospices Civils de Lyon | Nov 01, 2019 | - - |
HP:0000085 (present);na:HP:0000543 (present);na:HP:0000601 (present);na:HP:0001634 (present);na:HP:0002616 (present) Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Center for Personalized Medicine, Children's Hospital Los Angeles | Nov 19, 2018 | - - |
Inborn genetic diseases Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 04, 2022 | The c.607C>T (p.R203W) alteration is located in coding exon 4 of the PACS1 gene. This alteration results from a C to T substitution at nucleotide position 607, causing the arginine (R) at amino acid position 203 to be replaced by a tryptophan (W). Based on data from gnomAD, the T allele has an overall frequency of 0.001% (1/152152) total alleles studied. The highest observed frequency was 0.002% (1/41434) of African/African American alleles. This one allele was reported with low allele balance (0.2-0.25). This recurrent de novo alteration has been reported in multiple individuals with Schuurs-Hoeijmakers syndrome, with commonly reported features including developmental delay/intellectual disability, dysmorphic facial features, seizures, and other congenital malformations (Schurrs-Hoeijmakers, 2016; Deciphering Developmental Disorders Study, 2017; Stern, 2017; Gadzicki, 2015; Tenorio-Castaño, 2021). This amino acid position is highly conserved in available vertebrate species. The p.R203W substitution is positioned in the furin (cargo)-binding region of PACS1, which lies directly adjacent to the R196RKRY CK2-binding motif. This motif regulates phosphorylation status of the autoregulatory domain and PACS1 gene activation (Shuurs-Hoeijmakers, 2012). Functional analysis in zebrafish embryos with overexpression of mutant mRNA with this alteration demonstrated a significant reduction in cranial cartilaginous structures at the ventral aspect. In addition, overexpression of this altered protein resulted in defective migration of cranial-neural-crest cells in the head. Studies in human embryonic kidney cells demonstrated that expression of mutant PACS1 remains more stable than the wild-type protein leading to observed cellular aggregates (Shuurs-Hoeijmakers, 2012). The in silico prediction for this alteration is inconclusive. Based on the available evidence, this alteration is classified as pathogenic. - |
PACS1-related disorder Pathogenic:1
| Pathogenic, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 14, 2024 | The PACS1 c.607C>T variant is predicted to result in the amino acid substitution p.Arg203Trp. This variant has been reported as a recurrent de novo alteration in several individuals with Schuurs-Hoeijmakers syndrome and is considered one of the defining variants of this disorder (Schuurs-Hoeijmakers et al. 2012. PubMed ID: 23159249; Seto et al. 2020. PubMed ID: 33166031). This variant has not been reported in a large population database, indicating it is rare. This variant is interpreted as pathogenic. - |
PACS1-related syndrome Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Feb 05, 2020 | Across a selection of available literature, the PACS1 c.607C>T (p.Arg203Trp) missense variant has been found in a heterozygous state in at least 35 individuals with PACS1-related Syndrome (Schuurs-Hoeijmakers et al. 2012; Farwell et al. 2015; Schuurs-Hoeijmakers et al. 2016, Lazaridis et al. 2016; Stern et al. 2017; Tarailo-Graovac et al. 2017; Bowling et al. 2017; Geisheker et al. 2017; Pefkianaki et al. 2018; Dutta et al. 2019). This variant was identified as de novo in the affected individuals in all instances where parental samples were available. Control data are unavailable for this variant, which is absent from the Genome Aggregation Database in an area of good sequencing coverage, so the variant is presumed to be rare. Expression of the variant PACS1 mRNA in zebrafish embryos induced craniofacial defects (Schuurs-Hoeijmakers et al. 2012). The authors also showed that the p.Arg203Trp variant results in the formation of cytoplasmic aggregates and altered protein trafficking, and suggested a dominant-negative affect on the protein. Based on the collective evidence, the p.Arg203Trp variant is classified as pathogenic for PACS1-related syndrome. - |
See cases Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Dec 07, 2021 | ACMG classification criteria: PS3, PS4, PM2, PM6, PP2 - |
Neurodevelopmental disorder Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes | Nov 07, 2022 | - - |
Intellectual disability Pathogenic:1
| Pathogenic, criteria provided, single submitter | clinical testing | Génétique des Maladies du Développement, Hospices Civils de Lyon | Mar 08, 2021 | Recurrent pathogenics PACS1 variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Gain of sheet (P = 0.0221);.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at