Genetic Variant VSTM1:p.Ala232Gly (chr19-54040977-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_198481.4(VSTM1):c.695C>G(p.Ala232Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,609,720 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A232T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0018 ( 5 hom. )

Consequence

VSTM1
NM_198481.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.611

Publications

4 publications found

Variant links:

Genes affected

VSTM1 (HGNC:29455): (V-set and transmembrane domain containing 1) Predicted to enable cytokine activity. Predicted to be involved in immune system process and signal transduction. Predicted to be located in extracellular space. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

VSTM1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053269565).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198481.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VSTM1	NM_198481.4	MANE Select	c.695C>G	p.Ala232Gly	missense	Exon 9 of 9	NP_940883.2	Q6UX27-1
VSTM1	NM_001288792.2		c.602C>G	p.Ala201Gly	missense	Exon 8 of 8	NP_001275721.1	Q6UX27-2
VSTM1	NM_001288791.2		c.431C>G	p.Ala144Gly	missense	Exon 9 of 9	NP_001275720.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VSTM1	ENST00000338372.7	TSL:1 MANE Select	c.695C>G	p.Ala232Gly	missense	Exon 9 of 9	ENSP00000343366.2	Q6UX27-1
VSTM1	ENST00000376626.5	TSL:1	c.602C>G	p.Ala201Gly	missense	Exon 8 of 8	ENSP00000365813.1	Q6UX27-2
VSTM1	ENST00000366170.6	TSL:1	c.335C>G	p.Ala112Gly	missense	Exon 6 of 6	ENSP00000444153.2	D2DJS5

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

189

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00212

Gnomad OTH

AF:

0.000960

GnomAD2 exomes

AF:

0.00157

AC:

388

AN:

247146

AF XY:

0.00148

show subpopulations

Gnomad AFR exome

AF:

0.000442

Gnomad AMR exome

AF:

0.000501

Gnomad ASJ exome

AF:

0.00130

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00190

Gnomad NFE exome

AF:

0.00265

Gnomad OTH exome

AF:

0.00217

GnomAD4 exome

AF:

0.00182

AC:

2648

AN:

1457558

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

1312

AN XY:

725136

show subpopulations

African (AFR)

AF:

0.000151

AC:

AN:

33110

American (AMR)

AF:

0.000498

AC:

AN:

44198

Ashkenazi Jewish (ASJ)

AF:

0.00134

AC:

AN:

26042

East Asian (EAS)

AF:

0.00

AC:

AN:

39238

South Asian (SAS)

AF:

0.000151

AC:

AN:

85834

European-Finnish (FIN)

AF:

0.00178

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.000376

AC:

AN:

5324

European-Non Finnish (NFE)

AF:

0.00214

AC:

2380

AN:

1110302

Other (OTH)

AF:

0.00160

AC:

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

144

289

433

578

722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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:

0.00124

AC:

189

AN:

152162

Hom.:

Cov.:

AF XY:

0.000982

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41512

American (AMR)

AF:

0.000393

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00212

AC:

144

AN:

68010

Other (OTH)

AF:

0.000950

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.00165

Hom.:

Bravo

AF:

0.00119

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00175

AC:

212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.076

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.59

M_CAP

Benign

0.0043

MetaRNN

Benign

0.0053

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

0.61

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.2

REVEL

Benign

0.053

Sift

Uncertain

0.017

Sift4G

Uncertain

0.042

Polyphen

0.79

Vest4

0.092

MVP

0.048

MPC

0.19

ClinPred

0.0030

GERP RS

1.6

Varity_R

0.078

gMVP

0.061

Mutation Taster

=99/1

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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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