rs11461

Positions:

• chr10-124400865-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000274.4(OAT):​c.1134C>T​(p.Asn378Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,591,336 control chromosomes in the GnomAD database, including 126,448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (10447 hom., cov: 33)
  • Exomes 𝑓: 0.39 (116001 hom.)
• Consequence: OAT NM_000274.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.0870

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 10-124400865-G-A is Benign according to our data. Variant chr10-124400865-G-A is described in ClinVar as [Benign]. Clinvar id is 161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-124400865-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.087 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAT	NM_000274.4	c.1134C>T	p.Asn378Asn	synonymous_variant	9/10	ENST00000368845.6	NP_000265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAT	ENST00000368845.6	c.1134C>T	p.Asn378Asn	synonymous_variant	9/10	1	NM_000274.4	ENSP00000357838.5
OAT	ENST00000539214.5	c.720C>T	p.Asn240Asn	synonymous_variant	8/9	1		ENSP00000439042.1
OAT	ENST00000471127.1	n.644C>T		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52904 AN: 151948 Hom.: 10437 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.368

GnomAD3 exomes AF: 0.428 AC: 106738 AN: 249636 Hom.: 24507 AF XY: 0.428 AC XY: 57803 AN XY: 134966

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.587

Gnomad ASJ exome AF: 0.439

Gnomad EAS exome AF: 0.588

Gnomad SAS exome AF: 0.480

Gnomad FIN exome AF: 0.367

Gnomad NFE exome AF: 0.389

Gnomad OTH exome AF: 0.416

GnomAD4 exome AF: 0.393 AC: 565654 AN: 1439270 Hom.: 116001 Cov.: 31 AF XY: 0.396 AC XY: 284242 AN XY: 717084

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.577

Gnomad4 ASJ exome AF: 0.438

Gnomad4 EAS exome AF: 0.616

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.378

Gnomad4 OTH exome AF: 0.398

GnomAD4 genome AF: 0.348 AC: 52939 AN: 152066 Hom.: 10447 Cov.: 33 AF XY: 0.352 AC XY: 26199 AN XY: 74328

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.371

Alfa AF: 0.381 Hom.: 7311

Bravo AF: 0.346

Asia WGS AF: 0.522 AC: 1811 AN: 3478

EpiCase AF: 0.394

EpiControl AF: 0.383

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Ornithine aminotransferase deficiency Benign:6

Benign, no assertion criteria provided	literature only	OMIM	Feb 01, 1988	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 11, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 13, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.77
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs11461; hg19: chr10-126089434; COSMIC: COSV64347688; COSMIC: COSV64347688;