Genetic Variant VSTM2B:p.Gln158Glu (chr19-29529993-C-G) – 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_001146339.2(VSTM2B):c.472C>G(p.Gln158Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,390,568 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: not found (cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

VSTM2B
NM_001146339.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Publications

0 publications found

Variant links:

Genes affected

VSTM2B (HGNC:33595): (V-set and transmembrane domain containing 2B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

VSTM2B 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=0.22661555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSTM2B	NM_001146339.2 link	c.472C>G	p.Gln158Glu	missense_variant	Exon 4 of 5	ENST00000335523.8	NP_001139811.1	A6NLU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSTM2B	ENST00000335523.8 link	c.472C>G	p.Gln158Glu	missense_variant	Exon 4 of 5	5	NM_001146339.2	ENSP00000335038.6		A6NLU5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000216

AC:

AN:

1390568

Hom.:

Cov.:

AF XY:

0.00000292

AC XY:

AN XY:

686078

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31536

American (AMR)

AF:

0.00

AC:

AN:

35634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25124

East Asian (EAS)

AF:

0.00

AC:

AN:

35686

South Asian (SAS)

AF:

0.00

AC:

AN:

79090

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41720

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5590

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1078308

Other (OTH)

AF:

0.00

AC:

AN:

57880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000481

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.472C>G (p.Q158E) alteration is located in exon 4 (coding exon 4) of the VSTM2B gene. This alteration results from a C to G substitution at nucleotide position 472, causing the glutamine (Q) at amino acid position 158 to be replaced by a glutamic acid (E). 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

0.14

BayesDel_addAF

Benign

0.0028

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0069

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.23

MetaSVM

Uncertain

0.038

MutationAssessor

Uncertain

2.5

PhyloP100

1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.30

Sift

Uncertain

0.029

Sift4G

Benign

0.097

Polyphen

0.96

Vest4

0.072

MutPred

0.23

Loss of MoRF binding (P = 0.0514);

MVP

0.26

ClinPred

0.75

GERP RS

4.1

Varity_R

0.36

gMVP

0.42

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

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19-29529993-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over