Variant rs121965052 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong

The NM_000274.4(OAT):c.749G>T(p.Arg250Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R250P) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

OAT
NM_000274.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.82

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 links:

OAT (HGNC:):

OAT links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr10-124403820-C-G is described in Lovd as [Pathogenic].

PP3

MetaRNN computational evidence supports a deleterious effect, 0.975

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAT	NM_000274.4 linkuse as main transcript	c.749G>T	p.Arg250Leu	missense_variant	6/10	ENST00000368845.6	NP_000265.1	P04181-1A0A140VJQ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OAT	ENST00000368845.6 linkuse as main transcript	c.749G>T	p.Arg250Leu	missense_variant	6/10	1	NM_000274.4	ENSP00000357838.5	P04181-1
OAT	ENST00000539214.5 linkuse as main transcript	c.335G>T	p.Arg112Leu	missense_variant	5/9	1		ENSP00000439042.1	P04181-2
OAT	ENST00000467675.5 linkuse as main transcript	n.550G>T		non_coding_transcript_exon_variant	5/7	5
OAT	ENST00000483711.1 linkuse as main transcript	n.*25G>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727224

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:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.96

.;D

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Uncertain

0.29

MetaRNN

Pathogenic

0.98

D;D

MetaSVM

Uncertain

0.63

MutationAssessor

Pathogenic

3.3

.;M

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-5.8

D;D

REVEL

Pathogenic

0.73

Sift

Uncertain

0.016

D;D

Sift4G

Uncertain

0.018

D;D

Polyphen

0.25

.;B

Vest4

0.83

MutPred

0.84

.;Gain of stability (P = 0.0182);

MVP

0.94

MPC

0.73

ClinPred

1.0

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.89

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.26

Position offset: -22

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over