rs376556844

Variant names:

• chr12-29451515-C-A
• rs376556844
• NM_001353179.2:c.2690G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-29451515-C-A
• chr12-29451515-C-G
• chr12-29451515-C-T

Variant summary

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

The NM_001353179.2(OVCH1):​c.2690G>T​(p.Arg897Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 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. R897Q) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: OVCH1 NM_001353179.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

Genes affected

OVCH1 (HGNC:23080): (ovochymase 1) Predicted to enable metal ion binding activity and serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

OVCH1-AS1 (HGNC:44484): (OVCH1 antisense RNA 1)

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=0.07323399).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OVCH1	NM_001353179.2	c.2690G>T	p.Arg897Leu	missense_variant	Exon 22 of 26	ENST00000537054.2	NP_001340108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OVCH1	ENST00000537054.2	c.2690G>T	p.Arg897Leu	missense_variant	Exon 22 of 26	3	NM_001353179.2	ENSP00000445480.2
OVCH1	ENST00000318184.9	c.2585G>T	p.Arg862Leu	missense_variant	Exon 22 of 28	1		ENSP00000326708.5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152008 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152008 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74256

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.63
DANN	Benign	0.37
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.012	N
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.075
Sift	Benign	0.62	T
Sift4G	Benign	0.096	T
Vest4		0.17
MutPred		0.50		Gain of catalytic residue at R862 (P = 0.0222);
MVP		0.19
MPC		0.038
ClinPred		0.066	T
GERP RS		-2.0
gMVP		0.082

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

LitVar

Other links and lift over

dbSNP: rs376556844; hg19: chr12-29604448; COSMIC: COSV100549328;