Variant 10-49115463-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001031746.5(VSTM4):c.23C>T(p.Ala8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000294 in 1,035,376 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

VSTM4
NM_001031746.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.125

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008492529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VSTM4	NM_001031746.5 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	1/8	ENST00000332853.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSTM4	ENST00000332853.9 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	1/8	1	NM_001031746.5	P1	Q8IW00-1
VSTM4	ENST00000298454.3 linkuse as main transcript	c.23C>T	p.Ala8Val	missense_variant	1/3	2			Q8IW00-2

Frequencies

GnomAD3 genomes

AF:

0.00138

AC:

202

AN:

146862

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00447

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000812

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:

0.0000303

Gnomad OTH

AF:

0.00247

GnomAD3 exomes

AF:

0.000232

AC:

AN:

25916

Hom.:

AF XY:

0.000259

AC XY:

AN XY:

15458

show subpopulations

Gnomad AFR exome

AF:

0.00321

Gnomad AMR exome

AF:

0.000187

Gnomad ASJ exome

AF:

0.000928

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000150

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

AF:

0.000115

AC:

102

AN:

888408

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

420284

show subpopulations

Gnomad4 AFR exome

AF:

0.00479

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.000132

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000387

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000101

Gnomad4 OTH exome

AF:

0.000338

GnomAD4 genome

AF:

0.00137

AC:

202

AN:

146968

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

AN XY:

71568

show subpopulations

Gnomad4 AFR

AF:

0.00446

Gnomad4 AMR

AF:

0.000811

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000303

Gnomad4 OTH

AF:

0.00244

Alfa

AF:

0.000498

Hom.:

Bravo

AF:

0.00151

ExAC

AF:

0.000102

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.23C>T (p.A8V) alteration is located in exon 1 (coding exon 1) of the VSTM4 gene. This alteration results from a C to T substitution at nucleotide position 23, causing the alanine (A) at amino acid position 8 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.0064

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.35

T;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.0085

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.76

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.36

N;N

REVEL

Benign

0.017

Sift

Benign

0.67

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.24

MutPred

0.43

Loss of disorder (P = 0.0497);Loss of disorder (P = 0.0497);

MVP

0.030

MPC

0.16

ClinPred

0.013

GERP RS

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.040

gMVP

0.33

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over