X-108067084-C-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_182607.5(VSIG1):ā€‹c.362C>Gā€‹(p.Pro121Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,209,436 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 48 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000099 ( 0 hom., 3 hem., cov: 22)
Exomes š‘“: 0.00014 ( 0 hom. 45 hem. )

Consequence

VSIG1
NM_182607.5 missense

Scores

4
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.50
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 -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.33976644).
BS2
High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VSIG1NM_182607.5 linkc.362C>G p.Pro121Arg missense_variant Exon 3 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.362C>G p.Pro121Arg missense_variant Exon 3 of 7 1 NM_182607.5 ENSP00000217957.3 Q86XK7-1
VSIG1ENST00000415430.7 linkc.470C>G p.Pro157Arg missense_variant Exon 4 of 8 2 ENSP00000402219.3 Q86XK7-2
VSIG1ENST00000458383.1 linkc.470C>G p.Pro157Arg missense_variant Exon 4 of 4 4 ENSP00000407102.1 C9JY48
VSIG1ENST00000485533.1 linkn.198C>G non_coding_transcript_exon_variant Exon 2 of 4 5

Frequencies

GnomAD3 genomes
AF:
0.0000988
AC:
11
AN:
111370
Hom.:
0
Cov.:
22
AF XY:
0.0000893
AC XY:
3
AN XY:
33592
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:
0.000170
Gnomad OTH
AF:
0.00133
GnomAD3 exomes
AF:
0.0000982
AC:
18
AN:
183388
Hom.:
0
AF XY:
0.000103
AC XY:
7
AN XY:
67852
show subpopulations
Gnomad AFR exome
AF:
0.0000760
Gnomad AMR exome
AF:
0.000109
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:
0.000171
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000142
AC:
156
AN:
1098066
Hom.:
0
Cov.:
31
AF XY:
0.000124
AC XY:
45
AN XY:
363526
show subpopulations
Gnomad4 AFR exome
AF:
0.0000758
Gnomad4 AMR exome
AF:
0.000142
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:
0.000172
Gnomad4 OTH exome
AF:
0.0000868
GnomAD4 genome
AF:
0.0000988
AC:
11
AN:
111370
Hom.:
0
Cov.:
22
AF XY:
0.0000893
AC XY:
3
AN XY:
33592
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:
0.000170
Gnomad4 OTH
AF:
0.00133
Bravo
AF:
0.000178
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.000327
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.470C>G (p.P157R) alteration is located in exon 4 (coding exon 4) of the VSIG1 gene. This alteration results from a C to G substitution at nucleotide position 470, causing the proline (P) at amino acid position 157 to be replaced by an arginine (R). 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
Pathogenic
0.66
BayesDel_addAF
Uncertain
0.029
T
BayesDel_noAF
Uncertain
0.060
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
.;T;T
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.89
D;T;D
M_CAP
Pathogenic
0.44
D
MetaRNN
Benign
0.34
T;T;T
MetaSVM
Benign
-0.40
T
MutationAssessor
Uncertain
2.8
.;M;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Pathogenic
-5.4
D;D;D
REVEL
Uncertain
0.35
Sift
Uncertain
0.028
D;T;D
Sift4G
Pathogenic
0.0010
D;D;D
Polyphen
1.0
.;D;.
Vest4
0.77
MutPred
0.53
.;Loss of sheet (P = 0.1158);.;
MVP
0.15
MPC
0.76
ClinPred
0.49
T
GERP RS
5.2
Varity_R
0.46
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs202139574; hg19: chrX-107310314; COSMIC: COSV54261831; API