X-108077268-G-A

Variant summary

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

The NM_182607.5(VSIG1):​c.1051G>A​(p.Glu351Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000043 in 1,210,346 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 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 0.000027 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000045 ( 0 hom. 15 hem. )

Consequence

VSIG1
NM_182607.5 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.366
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.114783436).
BS2
High Hemizygotes in GnomAdExome4 at 15 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VSIG1NM_182607.5 linkc.1051G>A p.Glu351Lys 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
VSIG1ENST00000217957.10 linkc.1051G>A p.Glu351Lys missense_variant Exon 7 of 7 1 NM_182607.5 ENSP00000217957.3 Q86XK7-1
VSIG1ENST00000415430.7 linkc.1159G>A p.Glu387Lys missense_variant Exon 8 of 8 2 ENSP00000402219.3 Q86XK7-2

Frequencies

GnomAD3 genomes
AF:
0.0000268
AC:
3
AN:
112089
Hom.:
0
Cov.:
23
AF XY:
0.0000292
AC XY:
1
AN XY:
34243
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000563
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000109
AC:
2
AN:
183344
Hom.:
0
AF XY:
0.0000147
AC XY:
1
AN XY:
67820
show subpopulations
Gnomad AFR exome
AF:
0.0000760
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:
0.000221
GnomAD4 exome
AF:
0.0000446
AC:
49
AN:
1098257
Hom.:
0
Cov.:
31
AF XY:
0.0000413
AC XY:
15
AN XY:
363611
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000558
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.0000268
AC:
3
AN:
112089
Hom.:
0
Cov.:
23
AF XY:
0.0000292
AC XY:
1
AN XY:
34243
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000563
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000149
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 13, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1159G>A (p.E387K) alteration is located in exon 8 (coding exon 8) of the VSIG1 gene. This alteration results from a G to A substitution at nucleotide position 1159, causing the glutamic acid (E) at amino acid position 387 to be replaced by a lysine (K). 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
0.088
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
12
DANN
Benign
0.97
DEOGEN2
Benign
0.021
.;T
FATHMM_MKL
Benign
0.057
N
LIST_S2
Benign
0.55
T;T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
.;L
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.0
N;N
REVEL
Benign
0.056
Sift
Uncertain
0.0060
D;D
Sift4G
Uncertain
0.021
D;D
Polyphen
0.020
.;B
Vest4
0.24
MVP
0.076
MPC
0.21
ClinPred
0.082
T
GERP RS
1.1
Varity_R
0.11
gMVP
0.16

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.

Other links and lift over

dbSNP: rs369725236; hg19: chrX-107320498; COSMIC: COSV54260507; COSMIC: COSV54260507; API