rs386833602

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5

The NM_000274.4(OAT):​c.267C>A​(p.Asn89Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (no stars).

Frequency

Genomes: not found (cov: 31)

Consequence

OAT
NM_000274.4 missense

Scores

13
4
2

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.19
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM1
In a turn (size 3) in uniprot entity OAT_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_000274.4
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.994
PP5
Variant 10-124408898-G-T is Pathogenic according to our data. Variant chr10-124408898-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 56120.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-124408898-G-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OATNM_000274.4 linkuse as main transcriptc.267C>A p.Asn89Lys missense_variant 3/10 ENST00000368845.6 NP_000265.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OATENST00000368845.6 linkuse as main transcriptc.267C>A p.Asn89Lys missense_variant 3/101 NM_000274.4 ENSP00000357838 P1P04181-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Ornithine aminotransferase deficiency Pathogenic:1
Likely pathogenic, no assertion criteria providedliterature onlyJuha Muilu Group; Institute for Molecular Medicine Finland (FIMM)-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.96
D
Eigen
Pathogenic
0.74
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Pathogenic
0.97
D
M_CAP
Pathogenic
0.64
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
4.1
H
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.47
T
PROVEAN
Pathogenic
-5.6
D
REVEL
Pathogenic
0.89
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0010
D
Polyphen
0.99
D
Vest4
0.93
MutPred
0.96
Gain of methylation at N89 (P = 0.0132);
MVP
0.98
MPC
0.85
ClinPred
1.0
D
GERP RS
4.1
Varity_R
0.99
gMVP
0.97

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: rs386833602; hg19: chr10-126097467; API