Genetic Variant VSTM2L:p.Ala3Val (chr20-37903358-C-T) – 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.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
NM_080607.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

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:

Genome browser will be placed here

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=0.21906522).

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.8C>T	p.Ala3Val	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.8C>T	p.Ala3Val	missense	Exon 1 of 4	ENSP00000362560.4	Q96N03-1
VSTM2L	ENST00000954389.1		c.8C>T	p.Ala3Val	missense	Exon 1 of 4	ENSP00000624448.1
VSTM2L	ENST00000869290.1		c.8C>T	p.Ala3Val	missense	Exon 1 of 3	ENSP00000539349.1

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

African (AFR)

AF:

0.00

AC:

AN:

26478

American (AMR)

AF:

0.00

AC:

AN:

25354

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22948

East Asian (EAS)

AF:

0.00

AC:

AN:

27842

South Asian (SAS)

AF:

0.00

AC:

AN:

72624

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33018

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5488

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1048208

Other (OTH)

AF:

0.0000549

AC:

AN:

54632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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

AF:

0.00000658

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41428

American (AMR)

AF:

0.0000655

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67964

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

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

0.26

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0077

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

1.3

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.040

REVEL

Benign

0.066

Sift

Benign

0.42

Sift4G

Benign

0.080

Polyphen

0.98

Vest4

0.23

MutPred

0.24

Loss of sheet (P = 0.0126)

MVP

0.21

MPC

0.74

ClinPred

0.88

GERP RS

4.6

PromoterAI

-0.14

Neutral

(source)

Varity_R

0.15

gMVP

0.49

Mutation Taster

=71/29

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