dbSNP rs753977306: VSTM4:p.Ala254Ser (chr10-49048493-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001031746.5(VSTM4):c.760G>T(p.Ala254Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000347 in 1,441,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

VSTM4
NM_001031746.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.45

Variant links:

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]

VSTM4 links:

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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=0.24952763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSTM4	NM_001031746.5 link	c.760G>T	p.Ala254Ser	missense_variant	Exon 6 of 8	ENST00000332853.9	NP_001026916.2	Q8IW00-1
VSTM4	XM_017015827.3 link	c.760G>T	p.Ala254Ser	missense_variant	Exon 6 of 9		XP_016871316.1
VSTM4	XM_047424711.1 link	c.760G>T	p.Ala254Ser	missense_variant	Exon 6 of 9		XP_047280667.1
VSTM4	XR_001747052.3 link	n.797G>T		non_coding_transcript_exon_variant	Exon 6 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSTM4	ENST00000332853.9 link	c.760G>T	p.Ala254Ser	missense_variant	Exon 6 of 8	1	NM_001031746.5	ENSP00000331062.3		Q8IW00-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000864

AC:

AN:

231544

Hom.:

AF XY:

0.00000798

AC XY:

AN XY:

125280

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000347

AC:

AN:

1441034

Hom.:

Cov.:

AF XY:

0.00000419

AC XY:

AN XY:

716394

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000452

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000251

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.84

M_CAP

Benign

0.0015

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.41

REVEL

Benign

0.11

Sift

Benign

0.11

Sift4G

Benign

0.28

Polyphen

0.91

Vest4

0.41

MutPred

0.17

Gain of glycosylation at A254 (P = 0.0044);

MVP

0.46

MPC

0.30

ClinPred

0.60

GERP RS

6.2

Varity_R

0.094

gMVP

0.13

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over