chr12-29444226-A-G

Variant summary

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

The NM_001353179.2(OVCH1):ā€‹c.3041T>Cā€‹(p.Leu1014Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,612,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 32)
Exomes š‘“: 0.00011 ( 0 hom. )

Consequence

OVCH1
NM_001353179.2 missense

Scores

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.101
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=0.08762482).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OVCH1NM_001353179.2 linkuse as main transcriptc.3041T>C p.Leu1014Ser missense_variant 24/26 ENST00000537054.2 NP_001340108.1
OVCH1-AS1NR_073172.1 linkuse as main transcriptn.561-42660A>G 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.3041T>C p.Leu1014Ser missense_variant 24/263 NM_001353179.2 ENSP00000445480 P1
OVCH1-AS1ENST00000551108.2 linkuse as main transcriptn.561-42660A>G intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152064
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
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:
0.0000883
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000482
AC:
12
AN:
248706
Hom.:
0
AF XY:
0.0000445
AC XY:
6
AN XY:
134916
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:
0.000106
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000110
AC:
160
AN:
1460268
Hom.:
0
Cov.:
30
AF XY:
0.0000991
AC XY:
72
AN XY:
726444
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000672
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:
0.000140
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152064
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74276
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000657
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000883
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000149
Hom.:
0
Bravo
AF:
0.000128
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000244
AC:
2
ExAC
AF:
0.0000414
AC:
5
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

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 GeneticsFeb 15, 2023The c.2936T>C (p.L979S) alteration is located in exon 24 (coding exon 24) of the OVCH1 gene. This alteration results from a T to C substitution at nucleotide position 2936, causing the leucine (L) at amino acid position 979 to be replaced by a serine (S). 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
-0.17
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
9.9
DANN
Benign
0.77
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.0065
N
LIST_S2
Benign
0.29
.;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.088
T;T
MetaSVM
Benign
-0.78
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.63
N;N
REVEL
Benign
0.28
Sift
Benign
0.51
T;T
Sift4G
Uncertain
0.0090
D;D
Vest4
0.32
MVP
0.50
MPC
0.088
ClinPred
0.037
T
GERP RS
-0.076
gMVP
0.079

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: rs377140442; hg19: chr12-29597159; API