Variant X-108058064-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_182607.5(VSIG1):c.76A>G(p.Ile26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,208,402 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.000012 ( 0 hom. 5 hem. )

Consequence

VSIG1
NM_182607.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

Variant links:

Genes affected

VSIG1 (HGNC:28675): (V-set and immunoglobulin domain containing 1) This gene encodes a member of the junctional adhesion molecule (JAM) family. The encoded protein contains multiple glycosylation sites at the N-terminal region, and multiple phosphorylation sites and glutamic acid/proline (EP) repeats at the C-terminal region. The gene is expressed in normal stomach and testis, as well as in gastric, esophageal and ovarian cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

VSIG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0344854).

BS2

High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSIG1	NM_182607.5 link	c.76A>G	p.Ile26Val	missense_variant	Exon 2 of 7	ENST00000217957.10	NP_872413.1	Q86XK7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VSIG1	ENST00000217957.10 link	c.76A>G	p.Ile26Val	missense_variant	Exon 2 of 7	1	NM_182607.5	ENSP00000217957.3	Q86XK7-1
VSIG1	ENST00000415430.7 link	c.76A>G	p.Ile26Val	missense_variant	Exon 2 of 8	2		ENSP00000402219.3	Q86XK7-2
VSIG1	ENST00000458383.1 link	c.76A>G	p.Ile26Val	missense_variant	Exon 2 of 4	4		ENSP00000407102.1	C9JY48

Frequencies

GnomAD3 genomes

AF:

0.0000897

AC:

AN:

111448

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

33648

show subpopulations

Gnomad AFR

AF:

0.000327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000497

AC:

AN:

180967

Hom.:

AF XY:

0.0000457

AC XY:

AN XY:

65665

show subpopulations

Gnomad AFR exome

AF:

0.000688

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000119

AC:

AN:

1096902

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

362566

show subpopulations

Gnomad4 AFR exome

AF:

0.000494

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000897

AC:

AN:

111500

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

33710

show subpopulations

Gnomad4 AFR

AF:

0.000326

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.76A>G (p.I26V) alteration is located in exon 2 (coding exon 2) of the VSIG1 gene. This alteration results from a A to G substitution at nucleotide position 76, causing the isoleucine (I) at amino acid position 26 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

.;T;T

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.58

T;T;T

M_CAP

Benign

0.058

MetaRNN

Benign

0.034

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.92

L;L;.

PrimateAI

Benign

0.47

PROVEAN

Benign

0.020

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.71

T;T;T

Sift4G

Benign

0.22

T;T;T

Polyphen

0.45

.;B;.

Vest4

0.22

MVP

0.32

MPC

0.31

ClinPred

0.069

GERP RS

5.3

Varity_R

0.039

gMVP

0.47

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over