Variant X-108072811-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000217957.10(VSIG1):c.547G>A(p.Val183Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000419 in 1,208,643 control chromosomes in the GnomAD database, including 2 homozygotes. There are 192 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., 9 hem., cov: 22)

Exomes 𝑓: 0.00043 ( 2 hom. 183 hem. )

Consequence

VSIG1
ENST00000217957.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.294

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=0.016896963).

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIG1	NM_182607.5 linkuse as main transcript	c.547G>A	p.Val183Met	missense_variant	4/7	ENST00000217957.10	NP_872413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSIG1	ENST00000217957.10 linkuse as main transcript	c.547G>A	p.Val183Met	missense_variant	4/7	1	NM_182607.5	ENSP00000217957	P2	Q86XK7-1
VSIG1	ENST00000415430.7 linkuse as main transcript	c.655G>A	p.Val219Met	missense_variant	5/8	2		ENSP00000402219	A2	Q86XK7-2
VSIG1	ENST00000479635.1 linkuse as main transcript	n.16G>A		non_coding_transcript_exon_variant	1/2	3
VSIG1	ENST00000485533.1 linkuse as main transcript	n.383G>A		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

110677

Hom.:

Cov.:

AF XY:

0.000274

AC XY:

AN XY:

32901

show subpopulations

Gnomad AFR

AF:

0.0000330

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000290

Gnomad ASJ

AF:

0.000759

Gnomad EAS

AF:

0.000283

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00840

Gnomad NFE

AF:

0.000472

Gnomad OTH

AF:

0.000672

GnomAD3 exomes

AF:

0.000470

AC:

AN:

183040

Hom.:

AF XY:

0.000666

AC XY:

AN XY:

67524

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.000219

Gnomad ASJ exome

AF:

0.000803

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000158

Gnomad FIN exome

AF:

0.0000628

Gnomad NFE exome

AF:

0.000832

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000430

AC:

472

AN:

1097909

Hom.:

Cov.:

AF XY:

0.000504

AC XY:

183

AN XY:

363291

show subpopulations

Gnomad4 AFR exome

AF:

0.000265

Gnomad4 AMR exome

AF:

0.000171

Gnomad4 ASJ exome

AF:

0.000568

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000739

Gnomad4 FIN exome

AF:

0.0000741

Gnomad4 NFE exome

AF:

0.000443

Gnomad4 OTH exome

AF:

0.000825

GnomAD4 genome

AF:

0.000316

AC:

AN:

110734

Hom.:

Cov.:

AF XY:

0.000273

AC XY:

AN XY:

32968

show subpopulations

Gnomad4 AFR

AF:

0.0000329

Gnomad4 AMR

AF:

0.000289

Gnomad4 ASJ

AF:

0.000759

Gnomad4 EAS

AF:

0.000284

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000472

Gnomad4 OTH

AF:

0.000662

Alfa

AF:

0.000723

Hom.:

Bravo

AF:

0.000434

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000595

AC:

ExAC

AF:

0.000560

AC:

EpiCase

AF:

0.00120

EpiControl

AF:

0.00231

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.655G>A (p.V219M) alteration is located in exon 5 (coding exon 5) of the VSIG1 gene. This alteration results from a G to A substitution at nucleotide position 655, causing the valine (V) at amino acid position 219 to be replaced by a methionine (M). 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

0.13

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.90

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

.;T

FATHMM_MKL

Benign

0.0033

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.017

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.20

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.59

N;N

REVEL

Benign

0.075

Sift

Benign

0.038

D;T

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.99

.;D

Vest4

0.033

MVP

0.12

MPC

0.22

ClinPred

0.036

GERP RS

-6.3

Varity_R

0.045

gMVP

0.29

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