chr12-29443399-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001353179.2(OVCH1):​c.3224G>A​(p.Arg1075His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,611,556 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

OVCH1
NM_001353179.2 missense

Scores

16

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.110
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-AS1 (HGNC:44484): (OVCH1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.093667984).
BP6
Variant 12-29443399-C-T is Benign according to our data. Variant chr12-29443399-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2255197.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OVCH1NM_001353179.2 linkuse as main transcriptc.3224G>A p.Arg1075His missense_variant 25/26 ENST00000537054.2 NP_001340108.1
OVCH1-AS1NR_073172.1 linkuse as main transcriptn.561-43487C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OVCH1ENST00000537054.2 linkuse as main transcriptc.3224G>A p.Arg1075His missense_variant 25/263 NM_001353179.2 ENSP00000445480 P1
OVCH1-AS1ENST00000551108.2 linkuse as main transcriptn.561-43487C>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
151992
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
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
GnomAD3 exomes
AF:
0.0000565
AC:
14
AN:
247944
Hom.:
0
AF XY:
0.0000446
AC XY:
6
AN XY:
134584
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000234
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000279
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000889
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000240
AC:
35
AN:
1459446
Hom.:
0
Cov.:
30
AF XY:
0.0000248
AC XY:
18
AN XY:
726002
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000404
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152110
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000387
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.000273
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000331
AC:
4
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJun 03, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
1.4
DANN
Benign
0.68
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0092
N
LIST_S2
Benign
0.47
.;T
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.094
T;T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.36
N;N
REVEL
Benign
0.048
Sift
Benign
0.55
T;T
Sift4G
Benign
0.24
T;T
Vest4
0.19
MVP
0.19
MPC
0.037
ClinPred
0.0063
T
GERP RS
-0.45
gMVP
0.082

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs370805015; hg19: chr12-29596332; COSMIC: COSV100548585; API