Variant 20-37903358-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000373461.9(VSTM2L):c.8C>T(p.Ala3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000272 in 1,468,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

VSTM2L
ENST00000373461.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

VSTM2L (HGNC:16096): (V-set and transmembrane domain containing 2 like) Predicted to enable cell-cell adhesion mediator activity. Involved in negative regulation of neuron apoptotic process. Located in cytoplasm and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

VSTM2L links:

LOC124904896 (HGNC:):

LOC124904896 links:

Genome browser will be placed here

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=0.21906522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM2L	NM_080607.3 linkuse as main transcript	c.8C>T	p.Ala3Val	missense_variant	1/4	ENST00000373461.9	NP_542174.1	Q96N03-1
VSTM2L	XM_011528530.2 linkuse as main transcript	c.8C>T	p.Ala3Val	missense_variant	1/3		XP_011526832.1
LOC124904896	XR_007067576.1 linkuse as main transcript	n.3611+3261G>A		intron_variant
LOC124904896	XR_007067577.1 linkuse as main transcript	n.543+3261G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VSTM2L	ENST00000373461.9 linkuse as main transcript	c.8C>T	p.Ala3Val	missense_variant	1/4	1	NM_080607.3	ENSP00000362560.4	Q96N03-1
VSTM2L	ENST00000448944.1 linkuse as main transcript	c.8C>T	p.Ala3Val	missense_variant	1/3	3		ENSP00000406537.1	Q96N03-2
VSTM2L	ENST00000373459.4 linkuse as main transcript	c.8C>T	p.Ala3Val	missense_variant	1/2	3		ENSP00000362558.4	Q96N03-3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000228

AC:

AN:

1316592

Hom.:

Cov.:

AF XY:

0.00000308

AC XY:

AN XY:

649016

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:

0.00

Gnomad4 OTH exome

AF:

0.0000549

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Feb 06, 2023

The c.8C>T (p.A3V) alteration is located in exon 1 (coding exon 1) of the VSTM2L gene. This alteration results from a C to T substitution at nucleotide position 8, causing the alanine (A) at amino acid position 3 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

0.26

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0077

T;.;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.65

T;T;T

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L;L

MutationTaster

Benign

0.93

D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.040

N;D;N

REVEL

Benign

0.066

Sift

Benign

0.42

T;D;T

Sift4G

Benign

0.080

T;D;T

Polyphen

0.98

D;.;.

Vest4

0.23

MutPred

0.24

Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);

MVP

0.21

MPC

0.74

ClinPred

0.88

GERP RS

4.6

Varity_R

0.15

gMVP

0.49

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