12-118079534-C-A

Variant names:

• chr12-118079534-C-A
• rs774654305
• NM_019086.6:c.737G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019086.6(VSIG10):​c.737G>T​(p.Arg246Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,710 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. R246H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: VSIG10 NM_019086.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18567887).

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.737G>T	p.Arg246Leu	missense	Exon 4 of 9	NP_061959.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSIG10	ENST00000359236.10	TSL:1 MANE Select	c.737G>T	p.Arg246Leu	missense	Exon 4 of 9	ENSP00000352172.5	Q8N0Z9-1
	VSIG10	ENST00000965107.1		c.737G>T	p.Arg246Leu	missense	Exon 4 of 9	ENSP00000635166.1
	VSIG10	ENST00000538357.1	TSL:2	c.434G>T	p.Arg145Leu	missense	Exon 3 of 3	ENSP00000442861.1	F5H724

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461710 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727138

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111870

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.27
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.090
Sift	Benign	0.27	T
Sift4G	Uncertain	0.040	D
Polyphen		0.053	B
Vest4		0.33
MutPred		0.54		Gain of catalytic residue at R246 (P = 0)
MVP		0.067
MPC		0.32
ClinPred		0.62	D
GERP RS		-1.6
Varity_R		0.057
gMVP		0.46
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs774654305; hg19: chr12-118517339;