Variant X-108061497-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000217957.10(VSIG1):c.213+3296G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000664 in 1,053,508 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000066 ( 0 hom. 2 hem. )

Consequence

VSIG1
ENST00000217957.10 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.557

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14179555).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIG1	NM_182607.5 linkuse as main transcript	c.213+3296G>A		intron_variant		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.213+3296G>A		intron_variant		1	NM_182607.5	ENSP00000217957	P2	Q86XK7-1
VSIG1	ENST00000415430.7 linkuse as main transcript	c.283G>A	p.Ala95Thr	missense_variant	3/8	2		ENSP00000402219	A2	Q86XK7-2
VSIG1	ENST00000458383.1 linkuse as main transcript	c.283G>A	p.Ala95Thr	missense_variant	3/4	4		ENSP00000407102

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000175

AC:

AN:

114372

Hom.:

AF XY:

0.0000245

AC XY:

AN XY:

40860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000141

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000664

AC:

AN:

1053508

Hom.:

Cov.:

AF XY:

0.00000581

AC XY:

AN XY:

344404

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000602

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000488

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 19, 2023

The c.283G>A (p.A95T) alteration is located in exon 3 (coding exon 3) of the VSIG1 gene. This alteration results from a G to A substitution at nucleotide position 283, causing the alanine (A) at amino acid position 95 to be replaced by a threonine (T). 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

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.35

CADD

Benign

6.3

DANN

Benign

0.92

DEOGEN2

Benign

0.0054

.;T

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.42

T;T

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.14

T;T

MetaSVM

Uncertain

0.19

MutationTaster

Benign

0.61

D;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.070

N;N

REVEL

Benign

0.12

Sift

Benign

0.24

T;T

Sift4G

Benign

0.88

T;T

Vest4

0.38

MutPred

0.34

Gain of phosphorylation at A95 (P = 0.0675);Gain of phosphorylation at A95 (P = 0.0675);

MVP

0.22

MPC

0.19

ClinPred

0.055

GERP RS

-0.36

gMVP

0.44

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