X-108067095-C-G

Variant names:

• chrX-108067095-C-G
• NM_182607.5:c.373C>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_182607.5(VSIG1):​c.373C>G​(p.Leu125Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: VSIG1 NM_182607.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.91

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.009274006).
• BP6: Variant X-108067095-C-G is Benign according to our data. Variant chrX-108067095-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3468591.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSIG1	NM_182607.5	c.373C>G	p.Leu125Val	missense_variant	Exon 3 of 7	ENST00000217957.10	NP_872413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSIG1	ENST00000217957.10	c.373C>G	p.Leu125Val	missense_variant	Exon 3 of 7	1	NM_182607.5	ENSP00000217957.3
VSIG1	ENST00000415430.7	c.481C>G	p.Leu161Val	missense_variant	Exon 4 of 8	2		ENSP00000402219.3
VSIG1	ENST00000458383.1	c.481C>G	p.Leu161Val	missense_variant	Exon 4 of 4	4		ENSP00000407102.1
VSIG1	ENST00000485533.1	n.209C>G		non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 22, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0040
DANN	Benign	0.50
DEOGEN2	Benign	0.0099	.;T;T
FATHMM_MKL	Benign	0.0043	N
LIST_S2	Benign	0.30	T;T;T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.0093	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.0	.;N;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.52	N;N;N
REVEL	Benign	0.034
Sift	Benign	0.51	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0010	.;B;.
Vest4		0.19
MutPred		0.35		.;Gain of sheet (P = 0.1208);.;
MVP		0.27
MPC		0.19
ClinPred		0.079	T
GERP RS		-5.3
Varity_R		0.043
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-107310325;