NM_182607.5:c.491C>A

Variant names:

• chrX-108072755-C-A
• rs376545734
• NM_182607.5:c.491C>A

Variant summary

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

The NM_182607.5(VSIG1):​c.491C>A​(p.Ala164Glu) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: VSIG1 NM_182607.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041303188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSIG1	NM_182607.5	c.491C>A	p.Ala164Glu	missense_variant	Exon 4 of 7	ENST00000217957.10	NP_872413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSIG1	ENST00000217957.10	c.491C>A	p.Ala164Glu	missense_variant	Exon 4 of 7	1	NM_182607.5	ENSP00000217957.3
VSIG1	ENST00000415430.7	c.599C>A	p.Ala200Glu	missense_variant	Exon 5 of 8	2		ENSP00000402219.3
VSIG1	ENST00000485533.1	n.327C>A		non_coding_transcript_exon_variant	Exon 3 of 4	5
VSIG1	ENST00000479635.1	n.-41C>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1097096 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 362486

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.23
DANN	Benign	0.62
DEOGEN2	Benign	0.018	.;T
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.49	T;T
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	.;L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.21	N;N
REVEL	Benign	0.054
Sift	Benign	1.0	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.087	.;B
Vest4		0.13
MVP		0.030
MPC		0.23
ClinPred		0.034	T
GERP RS		0.88
Varity_R		0.053
gMVP		0.49

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

Other links and lift over

dbSNP: rs376545734; hg19: chrX-107315985;