10-49077318-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001031746.5(VSTM4):c.535G>A(p.Val179Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

VSTM4
NM_001031746.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.527

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06342745).

BP6

Variant 10-49077318-C-T is Benign according to our data. Variant chr10-49077318-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2490034.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
VSTM4	NM_001031746.5 linkuse as main transcript	c.535G>A	p.Val179Met	missense_variant	4/8	ENST00000332853.9
VSTM4	XM_017015827.3 linkuse as main transcript	c.535G>A	p.Val179Met	missense_variant	4/9
VSTM4	XM_047424711.1 linkuse as main transcript	c.535G>A	p.Val179Met	missense_variant	4/9
VSTM4	XR_001747052.3 linkuse as main transcript	n.572G>A		non_coding_transcript_exon_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSTM4	ENST00000332853.9 linkuse as main transcript	c.535G>A	p.Val179Met	missense_variant	4/8	1	NM_001031746.5	P1	Q8IW00-1
VSTM4	ENST00000476018.2 linkuse as main transcript			upstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251292

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.66

Cadd

Benign

7.3

Dann

Benign

0.97

DEOGEN2

Benign

0.011

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.80

M_CAP

Benign

0.0031

MetaRNN

Benign

0.063

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

MutationTaster

Benign

0.82

PrimateAI

Benign

0.30

PROVEAN

Benign

0.0

REVEL

Benign

0.021

Sift

Benign

0.19

Sift4G

Benign

0.12

Polyphen

0.0060

Vest4

0.25

MutPred

0.43

Gain of sheet (P = 0.0016);

MVP

0.081

MPC

0.17

ClinPred

0.089

GERP RS

-0.40

Varity_R

0.030

gMVP

0.22

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