Genetic Variant OVCH1:p.Ala916Pro (chr12-29451459-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.69

Publications

27 publications found

Variant links:

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 links:

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

OVCH1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OVCH1	NM_001353179.2 link	c.2746G>C	p.Ala916Pro	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 link	c.2746G>C	p.Ala916Pro	missense_variant	Exon 22 of 26	3	NM_001353179.2	ENSP00000445480.2
OVCH1	ENST00000318184.9 link	c.2641G>C	p.Ala881Pro	missense_variant	Exon 22 of 28	1		ENSP00000326708.5

Frequencies

GnomAD3 genomes

AF:

0.561

AC:

85138

AN:

151692

Hom.:

24221

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.544

AC XY:

395528

AN XY:

726716

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

20196

40392

60589

80785

100981

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17264

34528

51792

69056

86320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.561

AC:

85204

AN:

151810

Hom.:

24246

Cov.:

AF XY:

0.556

AC XY:

41268

AN XY:

74174

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1879

3758

5636

7515

9394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

726

1452

2178

2904

3630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

AlphaMissense

Benign

0.039

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.7

(source)

DANN

Benign

0.77

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.00043

MetaRNN

Benign

0.000015

MetaSVM

Benign

-0.96

PhyloP100

1.7

PrimateAI

Benign

0.29

PROVEAN

Benign

2.3

REVEL

Benign

0.043

Sift

Benign

0.68

Sift4G

Benign

1.0

Vest4

0.029

MPC

0.038

ClinPred

0.00040

GERP RS

2.4

gMVP

0.21

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over