Variant chr12-118066668-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019086.6(VSIG10):c.1594A>G(p.Ile532Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,612,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

VSIG10
NM_019086.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00200

Variant links:

Genes affected

VSIG10 (HGNC:26078): (V-set and immunoglobulin domain containing 10) Predicted to enable cell adhesion molecule binding activity. Predicted to be involved in cell-cell adhesion. Predicted to be active in cell-cell junction. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

VSIG10 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.027041525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VSIG10	NM_019086.6 linkuse as main transcript	c.1594A>G	p.Ile532Val	missense_variant	9/9	ENST00000359236.10
LOC124903030	XR_007063479.1 linkuse as main transcript	n.221+4988T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSIG10	ENST00000359236.10 linkuse as main transcript	c.1594A>G	p.Ile532Val	missense_variant	9/9	1	NM_019086.6	P1	Q8N0Z9-1
	ENST00000617135.1 linkuse as main transcript	n.271T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

246686

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

134042

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000901

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000822

AC:

AN:

1460712

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726566

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151984

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000731

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2024

The c.1594A>G (p.I532V) alteration is located in exon 9 (coding exon 9) of the VSIG10 gene. This alteration results from a A to G substitution at nucleotide position 1594, causing the isoleucine (I) at amino acid position 532 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.0

DANN

Benign

0.95

DEOGEN2

Benign

0.0010

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.53

M_CAP

Benign

0.0038

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.040

REVEL

Benign

0.078

Sift

Benign

0.33

Sift4G

Uncertain

0.058

Polyphen

0.0050

Vest4

0.050

MutPred

0.14

Loss of helix (P = 0.0558);

MVP

0.11

MPC

0.17

ClinPred

0.040

GERP RS

-0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.027

gMVP

0.064

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over