12-29461940-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001353179.2(OVCH1):ā€‹c.2299A>Gā€‹(p.Thr767Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,613,762 control chromosomes in the GnomAD database, including 3 homozygotes. 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‘“ 0.00060 ( 2 hom., cov: 33)
Exomes š‘“: 0.000050 ( 1 hom. )

Consequence

OVCH1
NM_001353179.2 missense

Scores

15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.213
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.015684783).
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OVCH1NM_001353179.2 linkuse as main transcriptc.2299A>G p.Thr767Ala missense_variant 19/26 ENST00000537054.2 NP_001340108.1
OVCH1-AS1NR_073172.1 linkuse as main transcriptn.561-24946T>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.2299A>G p.Thr767Ala missense_variant 19/263 NM_001353179.2 ENSP00000445480 P1
OVCH1-AS1ENST00000551108.2 linkuse as main transcriptn.561-24946T>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.000604
AC:
92
AN:
152222
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00602
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:
0.000233
AC:
58
AN:
248926
Hom.:
1
AF XY:
0.000185
AC XY:
25
AN XY:
135030
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00165
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:
0.000166
GnomAD4 exome
AF:
0.0000499
AC:
73
AN:
1461540
Hom.:
1
Cov.:
31
AF XY:
0.0000481
AC XY:
35
AN XY:
727062
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00157
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:
0.0000331
GnomAD4 genome
AF:
0.000604
AC:
92
AN:
152222
Hom.:
2
Cov.:
33
AF XY:
0.000766
AC XY:
57
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00602
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
Bravo
AF:
0.000574
ExAC
AF:
0.0000165
AC:
2

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 GeneticsSep 09, 2021The c.2194A>G (p.T732A) alteration is located in exon 19 (coding exon 19) of the OVCH1 gene. This alteration results from a A to G substitution at nucleotide position 2194, causing the threonine (T) at amino acid position 732 to be replaced by an alanine (A). 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
-0.39
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
1.4
DANN
Benign
0.60
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.012
N
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.016
T
MetaSVM
Benign
-0.82
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.19
Sift
Benign
0.95
T
Sift4G
Benign
0.087
T
Vest4
0.079
MutPred
0.40
Loss of phosphorylation at T732 (P = 0.1234);
MVP
0.43
MPC
0.035
ClinPred
0.020
T
GERP RS
-1.1
gMVP
0.44

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: rs758087927; hg19: chr12-29614873; API