dbSNP rs775005192: VSTM2B:p.Pro171Leu (chr19-29530033-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001146339.2(VSTM2B):c.512C>T(p.Pro171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000667 in 1,528,134 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 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

VSTM2B
NM_001146339.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3001122).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146339.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VSTM2B	NM_001146339.2	MANE Select	c.512C>T	p.Pro171Leu	missense	Exon 4 of 5	NP_001139811.1	A6NLU5
VSTM2B	NM_001384640.1		c.482C>T	p.Pro161Leu	missense	Exon 3 of 4	NP_001371569.1
VSTM2B	NM_001384641.1		c.374C>T	p.Pro125Leu	missense	Exon 4 of 5	NP_001371570.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VSTM2B	ENST00000335523.8	TSL:5 MANE Select	c.512C>T	p.Pro171Leu	missense	Exon 4 of 5	ENSP00000335038.6	A6NLU5
VSTM2B	ENST00000915703.1		c.584C>T	p.Pro195Leu	missense	Exon 6 of 7	ENSP00000585762.1
VSTM2B	ENST00000952478.1		c.578C>T	p.Pro193Leu	missense	Exon 5 of 6	ENSP00000622537.1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000908

AC:

AN:

121158

AF XY:

0.000105

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000343

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000439

Gnomad OTH exome

AF:

0.000265

GnomAD4 exome

AF:

0.0000661

AC:

AN:

1375956

Hom.:

Cov.:

AF XY:

0.0000722

AC XY:

AN XY:

678654

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30180

American (AMR)

AF:

0.000400

AC:

AN:

35004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24810

East Asian (EAS)

AF:

0.00

AC:

AN:

34694

South Asian (SAS)

AF:

0.00

AC:

AN:

77864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35886

Middle Eastern (MID)

AF:

0.000193

AC:

AN:

5176

European-Non Finnish (NFE)

AF:

0.0000614

AC:

AN:

1074906

Other (OTH)

AF:

0.000174

AC:

AN:

57436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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:

0.0000723

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41470

American (AMR)

AF:

0.000131

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.552

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000793

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

0.19

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Benign

0.15

Eigen_PC

Benign

0.061

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.90

MetaRNN

Benign

0.30

MetaSVM

Uncertain

0.12

MutationAssessor

Uncertain

2.5

PhyloP100

1.7

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-6.1

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.11

MutPred

0.21

Loss of glycosylation at P171 (P = 0.0265)

MVP

0.33

ClinPred

0.43

GERP RS

4.0

Varity_R

0.56

gMVP

0.66

Mutation Taster

=66/34

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over