12-118071382-T-C

Position:

• chr12-118071382-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_019086.6(VSIG10):​c.1307A>G​(p.Tyr436Cys) 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 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: VSIG10 NM_019086.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.29

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]

LOC124903030 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.837

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VSIG10	NM_019086.6	c.1307A>G	p.Tyr436Cys	missense_variant	6/9	ENST00000359236.10
LOC124903030	XR_007063479.1	n.222-4792T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSIG10	ENST00000359236.10	c.1307A>G	p.Tyr436Cys	missense_variant	6/9	1	NM_019086.6	P1
VSIG10	ENST00000545259.1	n.131A>G		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461644 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727104

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.1307A>G (p.Y436C) alteration is located in exon 6 (coding exon 6) of the VSIG10 gene. This alteration results from a A to G substitution at nucleotide position 1307, causing the tyrosine (Y) at amino acid position 436 to be replaced by a cysteine (C). 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	0.12
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.010	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	0.71	D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.29
Sift	Benign	0.22	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.89	P
Vest4		0.72
MutPred		0.67		Gain of catalytic residue at L433 (P = 0);
MVP		0.56
MPC		0.37
ClinPred		0.70	D
GERP RS		5.2
Varity_R		0.050
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1208586145; hg19: chr12-118509187;