NM_182607.5:c.1061C>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_182607.5(VSIG1):c.1061C>A(p.Thr354Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000967 in 1,210,321 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., 15 hem., cov: 23)

Exomes 𝑓: 0.000046 ( 0 hom. 12 hem. )

Consequence

VSIG1
NM_182607.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -2.21

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 Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055253804).

BP6

Variant X-108077278-C-A is Benign according to our data. Variant chrX-108077278-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 738138.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High Hemizygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSIG1	NM_182607.5 link	c.1061C>A	p.Thr354Lys	missense_variant	Exon 7 of 7	ENST00000217957.10	NP_872413.1	Q86XK7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSIG1	ENST00000217957.10 link	c.1061C>A	p.Thr354Lys	missense_variant	Exon 7 of 7	1	NM_182607.5	ENSP00000217957.3		Q86XK7-1
VSIG1	ENST00000415430.7 link	c.1169C>A	p.Thr390Lys	missense_variant	Exon 8 of 8	2		ENSP00000402219.3		Q86XK7-2

Frequencies

GnomAD3 genomes

AF:

0.000580

AC:

AN:

112020

Hom.:

Cov.:

AF XY:

0.000439

AC XY:

AN XY:

34174

show subpopulations

Gnomad AFR

AF:

0.00205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000946

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:

0.000668

GnomAD3 exomes

AF:

0.000153

AC:

AN:

183309

Hom.:

AF XY:

0.0000885

AC XY:

AN XY:

67803

show subpopulations

Gnomad AFR exome

AF:

0.00198

Gnomad AMR exome

AF:

0.0000729

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:

0.0000464

AC:

AN:

1098250

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

363610

show subpopulations

Gnomad4 AFR exome

AF:

0.00159

Gnomad4 AMR exome

AF:

0.0000852

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:

0.000130

GnomAD4 genome

AF:

0.000589

AC:

AN:

112071

Hom.:

Cov.:

AF XY:

0.000438

AC XY:

AN XY:

34235

show subpopulations

Gnomad4 AFR

AF:

0.00208

Gnomad4 AMR

AF:

0.0000945

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:

0.000659

Alfa

AF:

0.0000383

Hom.:

Bravo

AF:

0.000597

ESP6500AA

AF:

0.00261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000222

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1169C>A (p.T390K) alteration is located in exon 8 (coding exon 8) of the VSIG1 gene. This alteration results from a C to A substitution at nucleotide position 1169, causing the threonine (T) at amino acid position 390 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Apr 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.022

DANN

Benign

0.50

DEOGEN2

Benign

0.019

.;T

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.36

T;T

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.66

N;N

REVEL

Benign

0.0080

Sift

Benign

0.18

T;T

Sift4G

Uncertain

0.048

D;T

Polyphen

0.029

.;B

Vest4

0.20

MVP

0.030

MPC

0.22

ClinPred

0.013

GERP RS

-6.9

Varity_R

0.052

gMVP

0.13

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