20-63541272-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_080823.4(SRMS):​c.1204G>A​(p.Val402Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 34)

Consequence

SRMS
NM_080823.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.347
Variant links:
Genes affected
SRMS (HGNC:11298): (src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites) Enables protein tyrosine kinase activity. Involved in peptidyl-tyrosine autophosphorylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18658364).
BP6
Variant 20-63541272-C-T is Benign according to our data. Variant chr20-63541272-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3449366.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRMSNM_080823.4 linkc.1204G>A p.Val402Ile missense_variant Exon 7 of 8 ENST00000217188.2 NP_543013.1 Q9H3Y6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRMSENST00000217188.2 linkc.1204G>A p.Val402Ile missense_variant Exon 7 of 8 1 NM_080823.4 ENSP00000217188.1 Q9H3Y6

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Oct 16, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
0.34
DANN
Benign
0.91
DEOGEN2
Benign
0.11
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.055
N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.41
N
REVEL
Benign
0.15
Sift
Benign
0.18
T
Sift4G
Benign
0.48
T
Polyphen
0.0010
B
Vest4
0.044
MutPred
0.36
Gain of catalytic residue at S404 (P = 0.1056);
MVP
0.34
MPC
0.12
ClinPred
0.059
T
GERP RS
-5.1
Varity_R
0.049
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-62172625; API