Variant 19-54058468-C-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_198481.4(VSTM1):c.193G>T(p.Asp65Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000682 in 1,613,894 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 0.00042 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00071 ( 1 hom. )

Consequence

VSTM1
NM_198481.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0460

Variant links:

Genes affected

VSTM1 (HGNC:29455): (V-set and transmembrane domain containing 1) Predicted to enable cytokine activity. Predicted to be involved in immune system process and signal transduction. Predicted to be located in extracellular space. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

VSTM1 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=0.06485072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VSTM1	NM_198481.4 linkuse as main transcript	c.193G>T	p.Asp65Tyr	missense_variant	3/9	ENST00000338372.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSTM1	ENST00000338372.7 linkuse as main transcript	c.193G>T	p.Asp65Tyr	missense_variant	3/9	1	NM_198481.4	P2	Q6UX27-1

Frequencies

GnomAD3 genomes

AF:

0.000421

AC:

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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:

0.000735

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000421

AC:

106

AN:

251492

Hom.:

AF XY:

0.000397

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000844

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000709

AC:

1036

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000679

AC XY:

494

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.000890

Gnomad4 OTH exome

AF:

0.000430

GnomAD4 genome

AF:

0.000421

AC:

AN:

152002

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.000733

Hom.:

Bravo

AF:

0.000385

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000420

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000533

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

Apr 12, 2022

The c.193G>T (p.D65Y) alteration is located in exon 3 (coding exon 3) of the VSTM1 gene. This alteration results from a G to T substitution at nucleotide position 193, causing the aspartic acid (D) at amino acid position 65 to be replaced by a tyrosine (Y). 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

0.23

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.56

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.013

T;.;.;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.028

M_CAP

Benign

0.010

MetaRNN

Benign

0.065

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.5

M;M;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.0

D;D;D;.

REVEL

Benign

0.039

Sift

Benign

0.038

D;D;D;.

Sift4G

Benign

0.066

T;D;D;.

Polyphen

1.0

D;.;.;.

Vest4

0.38

MVP

0.095

MPC

0.57

ClinPred

0.061

GERP RS

-1.2

Varity_R

0.075

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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