rs763337946
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4BP7
This summary comes from the ClinGen Evidence Repository: The c.39A>G (p.Glu13Glu) variant in SOS1 is classified as likely benign because it does not alter an amino acid residue, is not located within the splice consensus site, and computational splice prediction tools do not predict an impact on splicing (BP4, BP7). It has been identified in 0.004165% (5/120058) of non-Finnish European chromosomes in gnomAD (BS1 not met; https://gnomad.broadinstitute.org). This variant was observed in several individuals with varying clinical presentations that lacked clear associations with a RASopathy. In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied: BP4, BP7. LINK:https://erepo.genome.network/evrepo/ui/classification/CA1624896/MONDO:0021060/004
Frequency
Consequence
NM_005633.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SOS1 | NM_005633.4 | c.39A>G | p.Glu13Glu | synonymous_variant | 1/23 | ENST00000402219.8 | NP_005624.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SOS1 | ENST00000402219.8 | c.39A>G | p.Glu13Glu | synonymous_variant | 1/23 | 1 | NM_005633.4 | ENSP00000384675.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000214 AC: 5AN: 233162Hom.: 0 AF XY: 0.0000234 AC XY: 3AN XY: 128000
GnomAD4 exome AF: 0.0000186 AC: 27AN: 1449570Hom.: 0 Cov.: 31 AF XY: 0.0000125 AC XY: 9AN XY: 721172
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74300
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | SOS1: BP4, BP7 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 21, 2015 | - - |
RASopathy Benign:2
Likely benign, reviewed by expert panel | curation | ClinGen RASopathy Variant Curation Expert Panel | Nov 04, 2019 | The c.39A>G (p.Glu13Glu) variant in SOS1 is classified as likely benign because it does not alter an amino acid residue, is not located within the splice consensus site, and computational splice prediction tools do not predict an impact on splicing (BP4, BP7). It has been identified in 0.004165% (5/120058) of non-Finnish European chromosomes in gnomAD (BS1 not met; https://gnomad.broadinstitute.org). This variant was observed in several individuals with varying clinical presentations that lacked clear associations with a RASopathy. In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied: BP4, BP7. - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 10, 2022 | - - |
Noonan syndrome and Noonan-related syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Aug 01, 2018 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 07, 2019 | This alteration is classified as likely 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