12-29451459-C-G

Position:

• chr12-29451459-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001353179.2(OVCH1):​c.2746G>C​(p.Ala916Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 1,612,712 control chromosomes in the GnomAD database, including 244,050 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.56 (24246 hom., cov: 31)
  • Exomes 𝑓: 0.55 (219804 hom.)
• Consequence: OVCH1 NM_001353179.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.5040328E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OVCH1	NM_001353179.2	c.2746G>C	p.Ala916Pro	missense_variant	22/26	ENST00000537054.2	NP_001340108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OVCH1	ENST00000537054.2	c.2746G>C	p.Ala916Pro	missense_variant	22/26	3	NM_001353179.2	ENSP00000445480.2
OVCH1	ENST00000318184.9	c.2641G>C	p.Ala881Pro	missense_variant	22/28	1		ENSP00000326708.5

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85138 AN: 151692 Hom.: 24221 Cov.: 31

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.585

GnomAD3 exomes AF: 0.516 AC: 127996 AN: 247980 Hom.: 34231 AF XY: 0.519 AC XY: 69750 AN XY: 134482

Gnomad AFR exome AF: 0.638

Gnomad AMR exome AF: 0.338

Gnomad ASJ exome AF: 0.594

Gnomad EAS exome AF: 0.414

Gnomad SAS exome AF: 0.478

Gnomad FIN exome AF: 0.575

Gnomad NFE exome AF: 0.560

Gnomad OTH exome AF: 0.547

GnomAD4 exome AF: 0.546 AC: 797624 AN: 1460902 Hom.: 219804 Cov.: 50 AF XY: 0.544 AC XY: 395528 AN XY: 726716

Gnomad4 AFR exome AF: 0.642

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.591

Gnomad4 EAS exome AF: 0.430

Gnomad4 SAS exome AF: 0.477

Gnomad4 FIN exome AF: 0.579

Gnomad4 NFE exome AF: 0.557

Gnomad4 OTH exome AF: 0.548

GnomAD4 genome AF: 0.561 AC: 85204 AN: 151810 Hom.: 24246 Cov.: 31 AF XY: 0.556 AC XY: 41268 AN XY: 74174

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.580

Alfa AF: 0.542 Hom.: 15886

Bravo AF: 0.556

TwinsUK AF: 0.560 AC: 2077

ALSPAC AF: 0.563 AC: 2169

ESP6500AA AF: 0.653 AC: 2456

ESP6500EA AF: 0.564 AC: 4638

ExAC AF: 0.522 AC: 63082

Asia WGS AF: 0.463 AC: 1605 AN: 3476

EpiCase AF: 0.555

EpiControl AF: 0.565

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.77
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.00043	N
MetaRNN	Benign	0.000015	T
MetaSVM	Benign	-0.96	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	2.3	N
REVEL	Benign	0.043
Sift	Benign	0.68	T
Sift4G	Benign	1.0	T
Vest4		0.029
MPC		0.038
ClinPred		0.00040	T
GERP RS		2.4
gMVP		0.21

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: rs1347570; hg19: chr12-29604392; COSMIC: COSV58959337;