rs1224646817

Variant names:

• chr12-118079428-C-A
• NM_019086.6:c.843G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-118079428-C-A
• chr12-118079428-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019086.6(VSIG10):​c.843G>T​(p.Gln281His) 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 benign outcome for this variant. 14/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: VSIG10 NM_019086.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10932207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSIG10	NM_019086.6	c.843G>T	p.Gln281His	missense_variant	Exon 4 of 9	ENST00000359236.10	NP_061959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSIG10	ENST00000359236.10	c.843G>T	p.Gln281His	missense_variant	Exon 4 of 9	1	NM_019086.6	ENSP00000352172.5
VSIG10	ENST00000538357.1	c.540G>T	p.Gln180His	missense_variant	Exon 3 of 3	2		ENSP00000442861.1
VSIG10	ENST00000545722.1	n.*26G>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461708 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727136

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0019	T;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.097
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.028
Sift	Benign	0.21	T;T
Sift4G	Uncertain	0.0050	D;.
Polyphen		0.082	B;.
Vest4		0.24
MutPred		0.29		Gain of sheet (P = 0.1208);.;
MVP		0.17
MPC		0.22
ClinPred		0.20	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.026
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-118517233;