chr10-124403003-C-T

Variant summary

Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong

The NM_000274.4(OAT):​c.824G>A​(p.Trp275*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Consequence

OAT
NM_000274.4 stop_gained

Scores

4
2
1

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:4

Conservation

PhyloP100: 3.75

Publications

2 publications found
Variant links:
Genes affected
OAT (HGNC:8091): (ornithine aminotransferase) This gene encodes the mitochondrial enzyme ornithine aminotransferase, which is a key enzyme in the pathway that converts arginine and ornithine into the major excitatory and inhibitory neurotransmitters glutamate and GABA. Mutations that result in a deficiency of this enzyme cause the autosomal recessive eye disease Gyrate Atrophy. Alternatively spliced transcript variants encoding different isoforms have been described. Related pseudogenes have been defined on the X chromosome. [provided by RefSeq, Jan 2010]
OAT Gene-Disease associations (from GenCC):
  • ornithine aminotransferase deficiency
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 18 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 10-124403003-C-T is Pathogenic according to our data. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124403003-C-T is described in CliVar as Pathogenic/Likely_pathogenic. Clinvar id is 180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OATNM_000274.4 linkc.824G>A p.Trp275* stop_gained Exon 7 of 10 ENST00000368845.6 NP_000265.1 P04181-1A0A140VJQ4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OATENST00000368845.6 linkc.824G>A p.Trp275* stop_gained Exon 7 of 10 1 NM_000274.4 ENSP00000357838.5 P04181-1
OATENST00000539214.5 linkc.410G>A p.Trp137* stop_gained Exon 6 of 9 1 ENSP00000439042.1 P04181-2
OATENST00000467675.5 linkn.625G>A non_coding_transcript_exon_variant Exon 6 of 7 5
OATENST00000471127.1 linkn.334G>A non_coding_transcript_exon_variant Exon 1 of 4 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251194
AF XY:
0.00
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0

ClinVar

Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Ornithine aminotransferase deficiency Pathogenic:4
Apr 06, 2023
Baylor Genetics
Significance:Likely pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Mar 31, 2022
Fulgent Genetics, Fulgent Genetics
Significance:Likely pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Sep 21, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This sequence change creates a premature translational stop signal (p.Trp275*) in the OAT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OAT are known to be pathogenic (PMID: 1737786, 23076989). This variant is present in population databases (rs267606924, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with OAT-related conditions. ClinVar contains an entry for this variant (Variation ID: 180). For these reasons, this variant has been classified as Pathogenic. -

Jan 29, 1993
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.59
CADD
Pathogenic
42
DANN
Uncertain
1.0
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Uncertain
0.93
D
PhyloP100
3.7
Vest4
0.97
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Mutation Taster
=1/199
disease causing (ClinVar)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs267606924; hg19: chr10-126091572; API