Genetic Variant VSTM2L:p.Val7Ala (chr20-37903370-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080607.3(VSTM2L):c.20T>C(p.Val7Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,327,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

VSTM2L
NM_080607.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.309

Publications

0 publications found

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:

ENSG00000305049 (HGNC:):

ENSG00000305049 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15498969).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080607.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM2L	NM_080607.3	MANE Select	c.20T>C	p.Val7Ala	missense	Exon 1 of 4	NP_542174.1	Q96N03-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VSTM2L	ENST00000373461.9	TSL:1 MANE Select	c.20T>C	p.Val7Ala	missense	Exon 1 of 4	ENSP00000362560.4	Q96N03-1
VSTM2L	ENST00000954389.1		c.20T>C	p.Val7Ala	missense	Exon 1 of 4	ENSP00000624448.1
VSTM2L	ENST00000869290.1		c.20T>C	p.Val7Ala	missense	Exon 1 of 3	ENSP00000539349.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

82324

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000151

AC:

AN:

1327496

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

654622

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26788

American (AMR)

AF:

0.00

AC:

AN:

27614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23374

East Asian (EAS)

AF:

0.0000704

AC:

AN:

28410

South Asian (SAS)

AF:

0.00

AC:

AN:

73916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5526

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1053440

Other (OTH)

AF:

0.00

AC:

AN:

55170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

Asia WGS

AF:

0.000292

AC:

AN:

3438

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0045

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.44

M_CAP

Benign

0.025

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.31

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.070

REVEL

Benign

0.075

Sift

Uncertain

0.010

Sift4G

Benign

0.53

Polyphen

0.81

Vest4

0.18

MutPred

0.37

Gain of helix (P = 6e-04)

MVP

0.25

MPC

0.25

ClinPred

0.18

GERP RS

-1.7

PromoterAI

0.052

Neutral

(source)

Varity_R

0.040

gMVP

0.31

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over