chr12-29451489-G-C

Variant summary

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

The NM_001353179.2(OVCH1):ā€‹c.2716C>Gā€‹(p.Leu906Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,102 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

OVCH1
NM_001353179.2 missense

Scores

1
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.390
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 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=0.17158002).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OVCH1NM_001353179.2 linkuse as main transcriptc.2716C>G p.Leu906Val missense_variant 22/26 ENST00000537054.2 NP_001340108.1
OVCH1-AS1NR_073172.1 linkuse as main transcriptn.561-35397G>C 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.2716C>G p.Leu906Val missense_variant 22/263 NM_001353179.2 ENSP00000445480 P1
OVCH1-AS1ENST00000551108.2 linkuse as main transcriptn.561-35397G>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
248332
Hom.:
0
AF XY:
0.0000223
AC XY:
3
AN XY:
134696
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000356
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461102
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
726830
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000248
AC:
3

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 submitterclinical testingAmbry GeneticsJan 06, 2023The c.2611C>G (p.L871V) alteration is located in exon 22 (coding exon 22) of the OVCH1 gene. This alteration results from a C to G substitution at nucleotide position 2611, causing the leucine (L) at amino acid position 871 to be replaced by a valine (V). 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
-0.31
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
8.6
DANN
Benign
0.96
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.14
N
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.88
N
REVEL
Benign
0.099
Sift
Benign
0.20
T
Sift4G
Pathogenic
0.0
D
Vest4
0.15
MutPred
0.53
Gain of MoRF binding (P = 0.1137);
MVP
0.51
MPC
0.23
ClinPred
0.33
T
GERP RS
3.0
gMVP
0.025

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.

Other links and lift over

dbSNP: rs753725091; hg19: chr12-29604422; API