Genetic Variant VSIG1:c.213+3296G>C (chrX-108061497-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001170553.2(VSIG1):c.283G>C(p.Ala95Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000019 in 1,053,509 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. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A95T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000019 ( 0 hom. 1 hem. )

Consequence

VSIG1
NM_001170553.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.557

Publications

2 publications found

Variant links:

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]

VSIG1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24509194).

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+3296G>C		intron	N/A	NP_872413.1	Q86XK7-1
	VSIG1	NM_001170553.2		c.283G>C	p.Ala95Pro	missense	Exon 3 of 8	NP_001164024.1	Q86XK7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VSIG1	ENST00000217957.10	TSL:1 MANE Select	c.213+3296G>C		intron	N/A	ENSP00000217957.3	Q86XK7-1
VSIG1	ENST00000415430.7	TSL:2	c.283G>C	p.Ala95Pro	missense	Exon 3 of 8	ENSP00000402219.3	Q86XK7-2
VSIG1	ENST00000458383.1	TSL:4	c.283G>C	p.Ala95Pro	missense	Exon 3 of 4	ENSP00000407102.1	C9JY48

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000874

AC:

AN:

114372

AF XY:

0.0000245

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000301

GnomAD4 exome

AF:

0.00000190

AC:

AN:

1053509

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

344405

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24860

American (AMR)

AF:

0.00

AC:

AN:

27902

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18612

East Asian (EAS)

AF:

0.00

AC:

AN:

27130

South Asian (SAS)

AF:

0.0000201

AC:

AN:

49854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37751

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4065

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

818922

Other (OTH)

AF:

0.0000225

AC:

AN:

44413

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Benign

-0.19

CADD

Benign

5.6

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0078

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.45

M_CAP

Pathogenic

0.44

MetaRNN

Benign

0.25

MetaSVM

Uncertain

0.56

PhyloP100

0.56

PrimateAI

Benign

0.38

PROVEAN

Benign

0.040

REVEL

Benign

0.28

Sift

Benign

0.14

Sift4G

Benign

0.12

Vest4

0.60

MutPred

0.53

Loss of sheet (P = 7e-04)

MVP

0.16

MPC

0.77

ClinPred

0.20

GERP RS

-0.36

gMVP

0.82

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over