12-29451459-C-G

Variant names:

• chr12-29451459-C-G
• rs1347570
• NM_001353179.2:c.2746G>C

Variant summary

Our verdict is Benign. The variant received -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. 14/18 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
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353179.2. 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
	OVCH1	NM_001353179.2	MANE Select	c.2746G>C	p.Ala916Pro	missense	Exon 22 of 26	NP_001340108.1	Q7RTY7-2
	OVCH1-AS1	NR_073170.1		n.561-10275C>G		intron	N/A
	OVCH1-AS1	NR_073171.1		n.561-10337C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OVCH1	ENST00000537054.2	TSL:3 MANE Select	c.2746G>C	p.Ala916Pro	missense	Exon 22 of 26	ENSP00000445480.2	Q7RTY7-2
	OVCH1	ENST00000318184.9	TSL:1	c.2641G>C	p.Ala881Pro	missense	Exon 22 of 28	ENSP00000326708.5	Q7RTY7-1
	OVCH1	ENST00000696934.1		n.2585G>C		non_coding_transcript_exon	Exon 16 of 22

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

GnomAD2 exomes AF: 0.516 AC: 127996 AN: 247980 AF XY: 0.519

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 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

African (AFR) AF: 0.642 AC: 21455 AN: 33442

American (AMR) AF: 0.352 AC: 15688 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 15434 AN: 26108

East Asian (EAS) AF: 0.430 AC: 17056 AN: 39678

South Asian (SAS) AF: 0.477 AC: 41139 AN: 86228

European-Finnish (FIN) AF: 0.579 AC: 30902 AN: 53366

Middle Eastern (MID) AF: 0.580 AC: 3341 AN: 5762

European-Non Finnish (NFE) AF: 0.557 AC: 619524 AN: 1111420

Other (OTH) AF: 0.548 AC: 33085 AN: 60336

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

African (AFR) AF: 0.637 AC: 26347 AN: 41372

American (AMR) AF: 0.437 AC: 6660 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2008 AN: 3464

East Asian (EAS) AF: 0.427 AC: 2193 AN: 5140

South Asian (SAS) AF: 0.473 AC: 2279 AN: 4818

European-Finnish (FIN) AF: 0.562 AC: 5917 AN: 10532

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37783 AN: 67932

Other (OTH) AF: 0.580 AC: 1226 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.039
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
PhyloP100		1.7
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
Mutation Taster		=96/4	polymorphism (auto)

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