Genetic Variant NM_000274.4:c.1312T>A (chr10-124397950-A-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP2

The NM_000274.4(OAT):c.1312T>A(p.Ser438Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S438S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

OAT
NM_000274.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.85

Publications

0 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: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

OAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 35 curated pathogenic missense variants (we use a threshold of 10). The gene has 4 curated benign missense variants. Gene score misZ: 0.87566 (below the threshold of 3.09). Trascript score misZ: 1.6556 (below the threshold of 3.09). GenCC associations: The gene is linked to ornithine aminotransferase deficiency.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000274.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OAT	NM_000274.4	MANE Select	c.1312T>A	p.Ser438Thr	missense	Exon 10 of 10	NP_000265.1	P04181-1
OAT	NM_001322965.2		c.1312T>A	p.Ser438Thr	missense	Exon 10 of 10	NP_001309894.1	P04181-1
OAT	NM_001322966.2		c.1312T>A	p.Ser438Thr	missense	Exon 11 of 11	NP_001309895.1	P04181-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OAT	ENST00000368845.6	TSL:1 MANE Select	c.1312T>A	p.Ser438Thr	missense	Exon 10 of 10	ENSP00000357838.5	P04181-1
OAT	ENST00000539214.5	TSL:1	c.898T>A	p.Ser300Thr	missense	Exon 9 of 9	ENSP00000439042.1	P04181-2
OAT	ENST00000921313.1		c.1315T>A	p.Ser439Thr	missense	Exon 10 of 10	ENSP00000591372.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Ornithine aminotransferase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.60

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.54

M_CAP

Uncertain

0.21

MetaRNN

Uncertain

0.46

MetaSVM

Uncertain

0.78

MutationAssessor

Benign

1.6

PhyloP100

8.8

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.49

Sift

Benign

0.16

Sift4G

Benign

0.19

Polyphen

0.0

Vest4

0.51

MutPred

0.37

Loss of disorder (P = 0.0672)

MVP

0.95

MPC

0.20

ClinPred

0.90

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.47

gMVP

0.73

Mutation Taster

=46/54

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over