chrX-108061509-C-T

Variant names:

• chrX-108061509-C-T
• rs1198549016
• NM_182607.5:c.213+3308C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001170553.2(VSIG1):​c.295C>T​(p.Arg99Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,164,527 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.000011 (0 hom. 3 hem.)
• Consequence: VSIG1 NM_001170553.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.39937705).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170553.2. 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.213+3308C>T		intron	N/A	NP_872413.1	Q86XK7-1
	VSIG1	NM_001170553.2		c.295C>T	p.Arg99Trp	missense	Exon 3 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.213+3308C>T		intron	N/A	ENSP00000217957.3	Q86XK7-1
	VSIG1	ENST00000415430.7	TSL:2	c.295C>T	p.Arg99Trp	missense	Exon 3 of 8	ENSP00000402219.3	Q86XK7-2
	VSIG1	ENST00000458383.1	TSL:4	c.295C>T	p.Arg99Trp	missense	Exon 3 of 4	ENSP00000407102.1	C9JY48

Frequencies

GnomAD3 genomes AF: 0.00000900 AC: 1 AN: 111172 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000952

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000114 AC: 12 AN: 1053355 Hom.: 0 Cov.: 29 AF XY: 0.00000871 AC XY: 3 AN XY: 344251

African (AFR) AF: 0.00 AC: 0 AN: 24856

American (AMR) AF: 0.00 AC: 0 AN: 27900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18611

East Asian (EAS) AF: 0.0000737 AC: 2 AN: 27128

South Asian (SAS) AF: 0.00 AC: 0 AN: 49848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4058

European-Non Finnish (NFE) AF: 0.0000122 AC: 10 AN: 818775

Other (OTH) AF: 0.00 AC: 0 AN: 44411

GnomAD4 genome AF: 0.00000900 AC: 1 AN: 111172 Hom.: 0 Cov.: 22 AF XY: 0.0000299 AC XY: 1 AN XY: 33420

African (AFR) AF: 0.00 AC: 0 AN: 30536

American (AMR) AF: 0.0000952 AC: 1 AN: 10504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3509

South Asian (SAS) AF: 0.00 AC: 0 AN: 2611

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52944

Other (OTH) AF: 0.00 AC: 0 AN: 1495

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	T
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.65	D
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	0.50	D
PhyloP100		2.3
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.012	D
Vest4		0.42
MutPred		0.55		Loss of disorder (P = 0.0206)
MVP		0.18
MPC		0.75
ClinPred		0.94	D
GERP RS		2.0
gMVP		0.67
Mutation Taster		=96/4	polymorphism

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: rs1198549016; hg19: chrX-107304739;