rs746267066

Variant names:

• chr20-63541486-C-T
• rs746267066
• NM_080823.4:c.1081G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-63541486-C-T
• chr20-63541486-C-A
• chr20-63541486-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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. 16/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13667181).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080823.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRMS	NM_080823.4	MANE Select	c.1081G>A	p.Gly361Ser	missense	Exon 6 of 8	NP_543013.1	Q9H3Y6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRMS	ENST00000217188.2	TSL:1 MANE Select	c.1081G>A	p.Gly361Ser	missense	Exon 6 of 8	ENSP00000217188.1	Q9H3Y6

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152080 Hom.: 0 Cov.: 34

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

GnomAD2 exomes AF: 0.0000124 AC: 3 AN: 241152 AF XY: 0.00000758

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 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

African (AFR) AF: 0.000239 AC: 8 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1111316

Other (OTH) AF: 0.0000332 AC: 2 AN: 60266

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152080 Hom.: 0 Cov.: 34 AF XY: 0.0000673 AC XY: 5 AN XY: 74286

African (AFR) AF: 0.000169 AC: 7 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.0000166 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.5
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
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs746267066; hg19: chr20-62172839; COSMIC: COSV53917301; COSMIC: COSV53917301;