20-63541486-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080823.4(SRMS):​c.1081G>A​(p.Gly361Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,608,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SRMS
NM_080823.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13667181).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRMSNM_080823.4 linkc.1081G>A p.Gly361Ser missense_variant Exon 6 of 8 ENST00000217188.2 NP_543013.1 Q9H3Y6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRMSENST00000217188.2 linkc.1081G>A p.Gly361Ser missense_variant Exon 6 of 8 1 NM_080823.4 ENSP00000217188.1 Q9H3Y6

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152080
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000124
AC:
3
AN:
241152
Hom.:
0
AF XY:
0.00000758
AC XY:
1
AN XY:
131908
show subpopulations
Gnomad AFR exome
AF:
0.000129
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000919
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1456090
Hom.:
0
Cov.:
34
AF XY:
0.0000138
AC XY:
10
AN XY:
724498
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000900
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152080
Hom.:
0
Cov.:
34
AF XY:
0.0000673
AC XY:
5
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000831
ExAC
AF:
0.0000166
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 01, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1081G>A (p.G361S) alteration is located in exon 6 (coding exon 6) of the SRMS gene. This alteration results from a G to A substitution at nucleotide position 1081, causing the glycine (G) at amino acid position 361 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
14
DANN
Benign
0.76
DEOGEN2
Benign
0.10
T
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.63
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.26
T
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.71
N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
0.73
N
REVEL
Benign
0.016
Sift
Benign
0.22
T
Sift4G
Benign
0.40
T
Polyphen
0.33
B
Vest4
0.22
MVP
0.27
MPC
0.17
ClinPred
0.061
T
GERP RS
3.5
Varity_R
0.048
gMVP
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs746267066; hg19: chr20-62172839; COSMIC: COSV53917301; COSMIC: COSV53917301; API