10-124405551-C-T

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_000274.4(OAT):c.533G>A(p.Trp178*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OAT
NM_000274.4 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 7.47

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

OAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 12 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 10-124405551-C-T is Pathogenic according to our data. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124405551-C-T is described in CliVar as Pathogenic. Clinvar id is 179.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OAT	NM_000274.4 link	c.533G>A	p.Trp178*	stop_gained	Exon 5 of 10	ENST00000368845.6	NP_000265.1	P04181-1A0A140VJQ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OAT	ENST00000368845.6 link	c.533G>A	p.Trp178*	stop_gained	Exon 5 of 10	1	NM_000274.4	ENSP00000357838.5	P04181-1
OAT	ENST00000539214.5 link	c.119G>A	p.Trp40*	stop_gained	Exon 4 of 9	1		ENSP00000439042.1	P04181-2
OAT	ENST00000467675.5 link	n.334G>A		non_coding_transcript_exon_variant	Exon 4 of 7	5
OAT	ENST00000483711.1 link	n.379G>A		non_coding_transcript_exon_variant	Exon 1 of 2	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461626

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111836

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Ornithine aminotransferase deficiency

Pathogenic:2

Mar 08, 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.Trp178*) 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 not present in population databases (gnomAD no frequency). 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: 179). 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

BayesDel_noAF

Pathogenic

0.65

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

1.0

PhyloP100

7.5

Vest4

0.94

GERP RS

4.6

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

Mutation Taster

=0/200

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over