chr20-63541272-C-T

Variant names:

• chr20-63541272-C-T
• NM_080823.4:c.1204G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_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. 17/22 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.347
• 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.

• 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 VariationId is 3449366.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1204G>A	p.Val402Ile	missense	Exon 7 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.1204G>A	p.Val402Ile	missense	Exon 7 of 8	ENSP00000217188.1	Q9H3Y6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.069
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
PhyloP100		-0.35
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
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

hg19: chr20-62172625;