chr10-49019757-T-A

Variant names:

• chr10-49019757-T-A
• NM_001031746.5:c.856A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001031746.5(VSTM4):​c.856A>T​(p.Asn286Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: VSTM4 NM_001031746.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.78
• Publications: 0 publications found

Genes affected

VSTM4 (HGNC:26470): (V-set and transmembrane domain containing 4) Predicted to act upstream of or within several processes, including endothelial cell migration; retina blood vessel maintenance; and vasculature development. Predicted to be located in extracellular region and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33353773).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031746.5. 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
	VSTM4	NM_001031746.5	MANE Select	c.856A>T	p.Asn286Tyr	missense	Exon 8 of 8	NP_001026916.2	Q8IW00-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM4	ENST00000332853.9	TSL:1 MANE Select	c.856A>T	p.Asn286Tyr	missense	Exon 8 of 8	ENSP00000331062.3	Q8IW00-1
	VSTM4	ENST00000956395.1		c.1069A>T	p.Asn357Tyr	missense	Exon 9 of 9	ENSP00000626454.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 34

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	Uncertain	0.41
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.8
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.099
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.019	D
Polyphen		0.80	P
Vest4		0.36
MutPred		0.37		Loss of loop (P = 0.0073)
MVP		0.24
MPC		0.52
ClinPred		0.95	D
GERP RS		5.9
Varity_R		0.19
gMVP		0.37
Mutation Taster		=70/30	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

hg19: chr10-50227802; COSMIC: COSV99066669; COSMIC: COSV99066669;