11-66070588-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_018026.4(PACS1):c.102G>A(p.Pro34=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00263 in 1,443,956 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 38 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 30 hom. )
Consequence
PACS1
NM_018026.4 synonymous
NM_018026.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0640
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=-0.75).
BP6
?
Variant 11-66070588-G-A is Benign according to our data. Variant chr11-66070588-G-A is described in ClinVar as [Benign]. Clinvar id is 129868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.064 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2091/151352) while in subpopulation AFR AF= 0.0472 (1955/41418). AF 95% confidence interval is 0.0455. There are 38 homozygotes in gnomad4. There are 978 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 2087 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PACS1 | NM_018026.4 | c.102G>A | p.Pro34= | synonymous_variant | 1/24 | ENST00000320580.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PACS1 | ENST00000320580.9 | c.102G>A | p.Pro34= | synonymous_variant | 1/24 | 1 | NM_018026.4 | P2 | |
PACS1 | ENST00000527224.1 | n.226G>A | non_coding_transcript_exon_variant | 1/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0138 AC: 2087AN: 151244Hom.: 38 Cov.: 32
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GnomAD3 exomes AF: 0.00166 AC: 153AN: 92258Hom.: 2 AF XY: 0.00117 AC XY: 62AN XY: 52768
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GnomAD4 exome AF: 0.00132 AC: 1712AN: 1292604Hom.: 30 Cov.: 31 AF XY: 0.00111 AC XY: 707AN XY: 638002
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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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 24, 2019 | - - |
Schuurs-Hoeijmakers syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at