12-118082184-C-T

Position:

• chr12-118082184-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_019086.6(VSIG10):​c.607G>A​(p.Ala203Thr) 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 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • 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: 2.50

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.92

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIG10	NM_019086.6	c.607G>A	p.Ala203Thr	missense_variant	3/9	ENST00000359236.10	NP_061959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSIG10	ENST00000359236.10	c.607G>A	p.Ala203Thr	missense_variant	3/9	1	NM_019086.6	ENSP00000352172	P1
VSIG10	ENST00000538357.1	c.362-2578G>A		intron_variant		2		ENSP00000442861
VSIG10	ENST00000545722.1	n.95G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461708 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727138

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

Apr 20, 2024

The c.607G>A (p.A203T) alteration is located in exon 3 (coding exon 3) of the VSIG10 gene. This alteration results from a G to A substitution at nucleotide position 607, causing the alanine (A) at amino acid position 203 to be replaced by a threonine (T). 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	Uncertain	0.39
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0094	T
MetaRNN	Pathogenic	0.92	D
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	0.98	D
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.21
Sift	Uncertain	0.012	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.59
MutPred		0.74		Gain of catalytic residue at L202 (P = 0);
MVP		0.46
MPC		0.75
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.18
gMVP		0.87

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: rs1362457747; hg19: chr12-118519989;