NM_182607.5:c.362C>T

Variant names:

• chrX-108067084-C-T
• rs202139574
• NM_182607.5:c.362C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182607.5(VSIG1):​c.362C>T​(p.Pro121Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,066 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts 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: 9.1e-7 (0 hom. 1 hem.)
• Consequence: VSIG1 NM_182607.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.50

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40997058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSIG1	NM_182607.5	c.362C>T	p.Pro121Leu	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.362C>T	p.Pro121Leu	missense_variant	Exon 3 of 7	1	NM_182607.5	ENSP00000217957.3
VSIG1	ENST00000415430.7	c.470C>T	p.Pro157Leu	missense_variant	Exon 4 of 8	2		ENSP00000402219.3
VSIG1	ENST00000458383.1	c.470C>T	p.Pro157Leu	missense_variant	Exon 4 of 4	4		ENSP00000407102.1
VSIG1	ENST00000485533.1	n.198C>T		non_coding_transcript_exon_variant	Exon 2 of 4	5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098066 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363526

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: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.22	.;T;T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Pathogenic	0.40	D
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.7	.;L;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Benign	0.29
Sift	Benign	0.76	T;T;T
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		0.78	.;P;.
Vest4		0.67
MutPred		0.56		.;Loss of catalytic residue at P121 (P = 0.0228);.;
MVP		0.16
MPC		0.57
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.27
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs202139574; hg19: chrX-107310314;