X-108072755-C-T

Position:

chrX-108072755-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_182607.5(VSIG1):c.491C>T(p.Ala164Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,207,950 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000015 ( 0 hom. 10 hem. )

Consequence

VSIG1
NM_182607.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.124

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:

VSIG1 (HGNC:):

VSIG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04476857).

BP6

Variant X-108072755-C-T is Benign according to our data. Variant chrX-108072755-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2529817.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIG1	NM_182607.5 linkuse as main transcript	c.491C>T	p.Ala164Val	missense_variant	4/7	ENST00000217957.10	NP_872413.1	Q86XK7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VSIG1	ENST00000217957.10 linkuse as main transcript	c.491C>T	p.Ala164Val	missense_variant	4/7	1	NM_182607.5	ENSP00000217957.3	Q86XK7-1
VSIG1	ENST00000415430.7 linkuse as main transcript	c.599C>T	p.Ala200Val	missense_variant	5/8	2		ENSP00000402219.3	Q86XK7-2
VSIG1	ENST00000485533.1 linkuse as main transcript	n.327C>T		non_coding_transcript_exon_variant	3/4	5
VSIG1	ENST00000479635.1 linkuse as main transcript	n.-41C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000361

AC:

AN:

110852

Hom.:

Cov.:

AF XY:

0.0000302

AC XY:

AN XY:

33074

show subpopulations

Gnomad AFR

AF:

0.0000988

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000545

AC:

AN:

183480

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

67914

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.000210

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000244

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000155

AC:

AN:

1097098

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

362486

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000924

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000107

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000361

AC:

AN:

110852

Hom.:

Cov.:

AF XY:

0.0000302

AC XY:

AN XY:

33074

show subpopulations

Gnomad4 AFR

AF:

0.0000988

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:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-1.1

CADD

Benign

2.2

DANN

Benign

0.82

DEOGEN2

Benign

0.034

.;T

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.060

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.74

.;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.015

Sift

Benign

0.35

T;T

Sift4G

Benign

0.45

T;T

Polyphen

0.068

.;B

Vest4

0.032

MutPred

0.44

.;Gain of glycosylation at T167 (P = 0.2857);

MVP

0.072

MPC

0.20

ClinPred

0.0086

GERP RS

0.88

Varity_R

0.035

gMVP

0.30

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