Genetic Variant NM_019086.6:c.1234G>T (chr12-118071455-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_019086.6(VSIG10):c.1234G>T(p.Gly412Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. G412R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

VSIG10
NM_019086.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.30

Publications

2 publications found

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:

LOC124903030 (HGNC:):

LOC124903030 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32136974).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019086.6. 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
	VSIG10	NM_019086.6	MANE Select	c.1234G>T	p.Gly412Trp	missense	Exon 6 of 9	NP_061959.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VSIG10	ENST00000359236.10	TSL:1 MANE Select	c.1234G>T	p.Gly412Trp	missense	Exon 6 of 9	ENSP00000352172.5	Q8N0Z9-1
VSIG10	ENST00000965107.1		c.1234G>T	p.Gly412Trp	missense	Exon 6 of 9	ENSP00000635166.1
VSIG10	ENST00000965105.1		c.973G>T	p.Gly325Trp	missense	Exon 5 of 8	ENSP00000635164.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248556

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111824

Other (OTH)

AF:

0.00

AC:

AN:

60368

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0089

Eigen

Benign

0.10

Eigen_PC

Benign

-0.052

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.79

M_CAP

Benign

0.075

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.4

PhyloP100

2.3

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.9

REVEL

Benign

0.26

Sift

Uncertain

0.013

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.46

MutPred

0.52

Gain of catalytic residue at G412 (P = 9e-04)

MVP

0.50

MPC

0.84

ClinPred

0.83

GERP RS

4.3

Varity_R

0.080

gMVP

0.78

Mutation Taster

=92/8

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over