rs397517170

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005633.4(SOS1):​c.373C>A​(p.Gln125Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q125Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

SOS1
NM_005633.4 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.87
Variant links:
Genes affected
SOS1 (HGNC:11187): (SOS Ras/Rac guanine nucleotide exchange factor 1) This gene encodes a protein that is a guanine nucleotide exchange factor for RAS proteins, membrane proteins that bind guanine nucleotides and participate in signal transduction pathways. GTP binding activates and GTP hydrolysis inactivates RAS proteins. The product of this gene may regulate RAS proteins by facilitating the exchange of GTP for GDP. Mutations in this gene are associated with gingival fibromatosis 1 and Noonan syndrome type 4. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SOS1NM_005633.4 linkuse as main transcriptc.373C>A p.Gln125Lys missense_variant 4/23 ENST00000402219.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SOS1ENST00000402219.8 linkuse as main transcriptc.373C>A p.Gln125Lys missense_variant 4/231 NM_005633.4 A1Q07889-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineOct 01, 2012- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.43
T;T;T;T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
.;D;D;D
M_CAP
Benign
0.047
D
MetaRNN
Uncertain
0.68
D;D;D;D
MetaSVM
Uncertain
-0.15
T
MutationAssessor
Benign
0.75
N;N;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.79
T
PROVEAN
Benign
-1.6
N;N;N;N
REVEL
Pathogenic
0.72
Sift
Benign
0.12
T;T;T;T
Sift4G
Benign
0.082
T;T;T;.
Polyphen
0.91
P;P;.;.
Vest4
0.59
MutPred
0.60
Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);.;
MVP
0.90
MPC
1.2
ClinPred
0.94
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.51
gMVP
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs397517170; hg19: chr2-39283980; API