Variant rs13088 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001031746.5(VSTM4):c.203T>C(p.Phe68Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,613,938 control chromosomes in the GnomAD database, including 142,856 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.48 ( 19390 hom., cov: 33)

Exomes 𝑓: 0.41 ( 123466 hom. )

Consequence

VSTM4
NM_001031746.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.870

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.616328E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VSTM4	NM_001031746.5 linkuse as main transcript	c.203T>C	p.Phe68Ser	missense_variant	2/8	ENST00000332853.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSTM4	ENST00000332853.9 linkuse as main transcript	c.203T>C	p.Phe68Ser	missense_variant	2/8	1	NM_001031746.5	P1	Q8IW00-1
VSTM4	ENST00000298454.3 linkuse as main transcript	c.203T>C	p.Phe68Ser	missense_variant	2/3	2			Q8IW00-2

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73668

AN:

151992

Hom.:

19362

Cov.:

show subpopulations

Gnomad AFR

AF:

0.704

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.475

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.463

GnomAD3 exomes

AF:

0.423

AC:

106238

AN:

251230

Hom.:

23899

AF XY:

0.420

AC XY:

57082

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.710

Gnomad AMR exome

AF:

0.446

Gnomad ASJ exome

AF:

0.447

Gnomad EAS exome

AF:

0.207

Gnomad SAS exome

AF:

0.485

Gnomad FIN exome

AF:

0.372

Gnomad NFE exome

AF:

0.401

Gnomad OTH exome

AF:

0.415

GnomAD4 exome

AF:

0.405

AC:

592248

AN:

1461826

Hom.:

123466

Cov.:

AF XY:

0.407

AC XY:

295650

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.714

Gnomad4 AMR exome

AF:

0.446

Gnomad4 ASJ exome

AF:

0.444

Gnomad4 EAS exome

AF:

0.220

Gnomad4 SAS exome

AF:

0.479

Gnomad4 FIN exome

AF:

0.376

Gnomad4 NFE exome

AF:

0.395

Gnomad4 OTH exome

AF:

0.412

GnomAD4 genome

AF:

0.485

AC:

73753

AN:

152112

Hom.:

19390

Cov.:

AF XY:

0.483

AC XY:

35923

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.704

Gnomad4 AMR

AF:

0.466

Gnomad4 ASJ

AF:

0.450

Gnomad4 EAS

AF:

0.219

Gnomad4 SAS

AF:

0.475

Gnomad4 FIN

AF:

0.366

Gnomad4 NFE

AF:

0.398

Gnomad4 OTH

AF:

0.458

Alfa

AF:

0.413

Hom.:

32931

Bravo

AF:

0.497

TwinsUK

AF:

0.389

AC:

1441

ALSPAC

AF:

0.394

AC:

1519

ESP6500AA

AF:

0.708

AC:

3121

ESP6500EA

AF:

0.393

AC:

3376

ExAC

AF:

0.429

AC:

52136

Asia WGS

AF:

0.396

AC:

1375

AN:

3478

EpiCase

AF:

0.395

EpiControl

AF:

0.405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.032

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.4

DANN

Benign

0.22

DEOGEN2

Benign

0.0041

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0097

LIST_S2

Benign

0.26

T;T

MetaRNN

Benign

0.0000026

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.30

PROVEAN

Benign

2.9

N;N

REVEL

Benign

0.043

Sift

Benign

0.97

T;T

Sift4G

Benign

0.77

T;T

Polyphen

0.0

B;B

Vest4

0.037

MPC

0.29

ClinPred

0.00051

GERP RS

1.8

Varity_R

0.025

gMVP

0.38

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