Variant 20-37944222-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_080607.3(VSTM2L):c.584G>A(p.Arg195His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,454,180 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 0.00024 ( 0 hom., cov: 26)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

VSTM2L
NM_080607.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.28

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:

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=0.12826693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM2L	NM_080607.3 linkuse as main transcript	c.584G>A	p.Arg195His	missense_variant	4/4	ENST00000373461.9	NP_542174.1
VSTM2L	XM_011528530.2 linkuse as main transcript	c.533G>A	p.Arg178His	missense_variant	3/3		XP_011526832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM2L	ENST00000373461.9 linkuse as main transcript	c.584G>A	p.Arg195His	missense_variant	4/4	1	NM_080607.3	ENSP00000362560	P1	Q96N03-1
VSTM2L	ENST00000373459.4 linkuse as main transcript	c.363G>A	p.Ala121=	synonymous_variant	2/2	3		ENSP00000362558		Q96N03-3

Frequencies

GnomAD3 genomes

AF:

0.000245

AC:

AN:

138840

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000296

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000445

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000127

AC:

AN:

133368

Hom.:

AF XY:

0.000139

AC XY:

AN XY:

71694

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000423

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000714

Gnomad NFE exome

AF:

0.000231

Gnomad OTH exome

AF:

0.000511

GnomAD4 exome

AF:

0.000295

AC:

388

AN:

1315340

Hom.:

Cov.:

AF XY:

0.000308

AC XY:

198

AN XY:

643740

show subpopulations

Gnomad4 AFR exome

AF:

0.000101

Gnomad4 AMR exome

AF:

0.0000303

Gnomad4 ASJ exome

AF:

0.000456

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000489

Gnomad4 NFE exome

AF:

0.000351

Gnomad4 OTH exome

AF:

0.000228

GnomAD4 genome

AF:

0.000245

AC:

AN:

138840

Hom.:

Cov.:

AF XY:

0.000224

AC XY:

AN XY:

66904

show subpopulations

Gnomad4 AFR

AF:

0.000107

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000296

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000445

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000407

Hom.:

ExAC

AF:

0.0000544

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

Jan 18, 2023

The c.584G>A (p.R195H) alteration is located in exon 4 (coding exon 4) of the VSTM2L gene. This alteration results from a G to A substitution at nucleotide position 584, causing the arginine (R) at amino acid position 195 to be replaced by a histidine (H). 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

0.33

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.031

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.0

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.25

REVEL

Benign

0.20

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.018

Polyphen

1.0

Vest4

0.41

MVP

0.17

MPC

0.81

ClinPred

0.24

GERP RS

4.2

Varity_R

0.10

gMVP

0.54

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