rs572697
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_018026.4(PACS1):c.2061T>A(p.Ser687=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,614,152 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 39 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 37 hom. )
Consequence
PACS1
NM_018026.4 synonymous
NM_018026.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.60
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant 11-66234199-T-A is Benign according to our data. Variant chr11-66234199-T-A is described in ClinVar as [Benign]. Clinvar id is 129870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-3.6 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0137 (2083/152316) while in subpopulation AFR AF= 0.0468 (1945/41570). AF 95% confidence interval is 0.0451. There are 39 homozygotes in gnomad4. There are 976 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 2083 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PACS1 | NM_018026.4 | c.2061T>A | p.Ser687= | synonymous_variant | 17/24 | ENST00000320580.9 | |
PACS1 | XM_011545162.2 | c.1767T>A | p.Ser589= | synonymous_variant | 17/24 | ||
PACS1 | XM_011545164.3 | c.1722T>A | p.Ser574= | synonymous_variant | 17/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PACS1 | ENST00000320580.9 | c.2061T>A | p.Ser687= | synonymous_variant | 17/24 | 1 | NM_018026.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0137 AC: 2079AN: 152198Hom.: 39 Cov.: 32
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GnomAD3 exomes AF: 0.00348 AC: 875AN: 251492Hom.: 20 AF XY: 0.00242 AC XY: 329AN XY: 135922
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GnomAD4 exome AF: 0.00140 AC: 2040AN: 1461836Hom.: 37 Cov.: 31 AF XY: 0.00116 AC XY: 844AN XY: 727224
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GnomAD4 genome ? AF: 0.0137 AC: 2083AN: 152316Hom.: 39 Cov.: 32 AF XY: 0.0131 AC XY: 976AN XY: 74482
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 14, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Schuurs-Hoeijmakers syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 24, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at