Variant 20-37944178-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000373461.9(VSTM2L):c.540G>A(p.Ala180Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,517,390 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

VSTM2L
ENST00000373461.9 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.463

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 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=0.010819346).

BP6

Variant 20-37944178-G-A is Benign according to our data. Variant chr20-37944178-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652309.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM2L	NM_080607.3 linkuse as main transcript	c.540G>A	p.Ala180Ala	synonymous_variant	4/4	ENST00000373461.9	NP_542174.1	Q96N03-1
VSTM2L	XM_011528530.2 linkuse as main transcript	c.489G>A	p.Ala163Ala	synonymous_variant	3/3		XP_011526832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VSTM2L	ENST00000373461.9 linkuse as main transcript	c.540G>A	p.Ala180Ala	synonymous_variant	4/4	1	NM_080607.3	ENSP00000362560.4	Q96N03-1
VSTM2L	ENST00000373459.4 linkuse as main transcript	c.319G>A	p.Ala107Thr	missense_variant	2/2	3		ENSP00000362558.4	Q96N03-3
VSTM2L	ENST00000448944.1 linkuse as main transcript	c.*42G>A		downstream_gene_variant		3		ENSP00000406537.1	Q96N03-2

Frequencies

GnomAD3 genomes

AF:

0.000148

AC:

AN:

141574

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000711

Gnomad ASJ

AF:

0.00508

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000245

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000308

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000257

AC:

AN:

151872

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

82454

show subpopulations

Gnomad AFR exome

AF:

0.000137

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00307

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000132

Gnomad NFE exome

AF:

0.000138

Gnomad OTH exome

AF:

0.000704

GnomAD4 exome

AF:

0.000121

AC:

166

AN:

1375732

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

676940

show subpopulations

Gnomad4 AFR exome

AF:

0.0000639

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00452

Gnomad4 EAS exome

AF:

0.0000286

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000173

Gnomad4 NFE exome

AF:

0.0000282

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000148

AC:

AN:

141658

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

68920

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000710

Gnomad4 ASJ

AF:

0.00508

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000245

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000308

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000320

Hom.:

ExAC

AF:

0.0000483

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

VSTM2L: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.8

DANN

Benign

0.87

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.28

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.76

MutationTaster

Benign

1.0

D;D;N

PROVEAN

Benign

-0.52

REVEL

Benign

0.038

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.23

MutPred

0.16

Gain of phosphorylation at A107 (P = 2e-04);

MVP

0.014

ClinPred

0.022

GERP RS

0.48

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