X-108073347-C-A

Variant names:

• chrX-108073347-C-A
• rs764140353
• NM_182607.5:c.666C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_182607.5(VSIG1):​c.666C>A​(p.Cys222*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,696 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. C222C) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: VSIG1 NM_182607.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182607.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSIG1	NM_182607.5	MANE Select	c.666C>A	p.Cys222*	stop_gained	Exon 5 of 7	NP_872413.1	Q86XK7-1
	VSIG1	NM_001170553.2		c.774C>A	p.Cys258*	stop_gained	Exon 6 of 8	NP_001164024.1	Q86XK7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSIG1	ENST00000217957.10	TSL:1 MANE Select	c.666C>A	p.Cys222*	stop_gained	Exon 5 of 7	ENSP00000217957.3	Q86XK7-1
	VSIG1	ENST00000415430.7	TSL:2	c.774C>A	p.Cys258*	stop_gained	Exon 6 of 8	ENSP00000402219.3	Q86XK7-2
	VSIG1	ENST00000479635.1	TSL:3	n.135C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096696 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 362126

African (AFR) AF: 0.00 AC: 0 AN: 26358

American (AMR) AF: 0.00 AC: 0 AN: 35100

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19357

East Asian (EAS) AF: 0.00 AC: 0 AN: 30132

South Asian (SAS) AF: 0.00 AC: 0 AN: 53749

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40503

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841338

Other (OTH) AF: 0.00 AC: 0 AN: 46027

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	26
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.47	N
PhyloP100		-0.049
Vest4		0.45
GERP RS		-2.0
Mutation Taster		=26/174	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs764140353; hg19: chrX-107316577;