Variant chr12-29444161-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001353179.2(OVCH1):c.3106C>T(p.His1036Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,607,290 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

OVCH1
NM_001353179.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.84

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 made for transcript

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=0.12956595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OVCH1	NM_001353179.2 linkuse as main transcript	c.3106C>T	p.His1036Tyr	missense_variant	24/26	ENST00000537054.2	NP_001340108.1
OVCH1-AS1	NR_073172.1 linkuse as main transcript	n.561-42725G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OVCH1	ENST00000537054.2 linkuse as main transcript	c.3106C>T	p.His1036Tyr	missense_variant	24/26	3	NM_001353179.2	ENSP00000445480	P1
OVCH1-AS1	ENST00000551108.2 linkuse as main transcript	n.561-42725G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

243392

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

132050

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.0000301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1455288

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723796

show subpopulations

Gnomad4 AFR exome

AF:

0.000181

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152002

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 27, 2023

The c.3001C>T (p.H1001Y) alteration is located in exon 24 (coding exon 24) of the OVCH1 gene. This alteration results from a C to T substitution at nucleotide position 3001, causing the histidine (H) at amino acid position 1001 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.7

DANN

Benign

0.37

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.48

.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.78

N;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T

Sift4G

Pathogenic

0.0

D;D

Vest4

0.36

MutPred

0.65

Loss of disorder (P = 0.0534);.;

MVP

0.39

MPC

0.037

ClinPred

0.065

GERP RS

1.6

gMVP

0.093

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over