rs139592595
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
This summary comes from the ClinGen Evidence Repository: The filtering allele frequency of the c.73C>T (p.Pro25Ser) variant in the SOS1 gene is 0.23% for African chromosomes by the Exome Aggregation Consortium (21/6116 with 95% CI), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert panel for autosomal dominant RASopathy variants (BA1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA181527/MONDO:0021060/004
Frequency
Consequence
NM_005633.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOS1 | NM_005633.4 | c.73C>T | p.Pro25Ser | missense_variant | 1/23 | ENST00000402219.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOS1 | ENST00000402219.8 | c.73C>T | p.Pro25Ser | missense_variant | 1/23 | 1 | NM_005633.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000783 AC: 119AN: 152064Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000144 AC: 32AN: 222176Hom.: 0 AF XY: 0.0000570 AC XY: 7AN XY: 122790
GnomAD4 exome AF: 0.0000654 AC: 94AN: 1437150Hom.: 0 Cov.: 31 AF XY: 0.0000559 AC XY: 40AN XY: 714948
GnomAD4 genome ? AF: 0.000789 AC: 120AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.000780 AC XY: 58AN XY: 74384
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 18, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 19, 2012 | p.Pro25Ser in Exon 01 of SOS1: This variant is not expected to have clinical sig nificance because it has been identified in 0.3% (12/3732) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs139592595). - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 11, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2022 | SOS1: BS1, BS2 - |
RASopathy Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Benign, reviewed by expert panel | curation | ClinGen RASopathy Variant Curation Expert Panel | Apr 03, 2017 | The filtering allele frequency of the c.73C>T (p.Pro25Ser) variant in the SOS1 gene is 0.23% for African chromosomes by the Exome Aggregation Consortium (21/6116 with 95% CI), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert panel for autosomal dominant RASopathy variants (BA1). - |
SOS1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 07, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Noonan syndrome 4;C4551558:Fibromatosis, gingival, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 18, 2021 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 26, 2019 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at