rs150939128

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 1P and 2B. PP2BP4_Moderate

The NM_000274.4(OAT):c.355G>A(p.Val119Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000403 in 1,612,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

OAT
NM_000274.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.49

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

OAT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.098863244).

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.355G>A	p.Val119Ile	missense	Exon 3 of 10	NP_000265.1	P04181-1
OAT	NM_001322965.2		c.355G>A	p.Val119Ile	missense	Exon 3 of 10	NP_001309894.1	P04181-1
OAT	NM_001322966.2		c.355G>A	p.Val119Ile	missense	Exon 4 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.355G>A	p.Val119Ile	missense	Exon 3 of 10	ENSP00000357838.5	P04181-1
OAT	ENST00000539214.5	TSL:1	c.-60G>A		5_prime_UTR	Exon 2 of 9	ENSP00000439042.1	P04181-2
OAT	ENST00000921313.1		c.355G>A	p.Val119Ile	missense	Exon 3 of 10	ENSP00000591372.1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000556

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000597

AC:

AN:

251344

AF XY:

0.0000662

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000281

AC:

AN:

1460104

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

726382

show subpopulations

African (AFR)

AF:

0.000987

AC:

AN:

33434

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

86180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4568

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111738

Other (OTH)

AF:

0.0000332

AC:

AN:

60242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000158

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.000554

AC:

AN:

41526

American (AMR)

AF:

0.0000655

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.000196

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Ornithine aminotransferase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.58

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.029

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.038

MetaRNN

Benign

0.099

MetaSVM

Benign

-0.37

MutationAssessor

Benign

1.3

PhyloP100

4.5

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.80

REVEL

Benign

0.29

Sift

Benign

0.14

Sift4G

Benign

0.25

Polyphen

0.0030

Vest4

0.22

MVP

0.84

MPC

0.20

ClinPred

0.042

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.34

gMVP

0.79

Mutation Taster

=192/108

polymorphism

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over