rs2459216

chr10-124397757-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000274.4(OAT):c.*185C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0733 in 613,082 control chromosomes in the GnomAD database, including 2,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1072 hom., cov: 33)
  • Exomes 𝑓: 0.064 (1142 hom.)
• Consequence: OAT NM_000274.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.01

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-124397757-G-A is Benign according to our data. Variant chr10-124397757-G-A is described in ClinVar as [Benign]. Clinvar id is 299166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAT	NM_000274.4	c.*185C>T		3_prime_UTR_variant	10/10	ENST00000368845.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAT	ENST00000368845.6	c.*185C>T		3_prime_UTR_variant	10/10	1	NM_000274.4	P1
OAT	ENST00000539214.5	c.*185C>T		3_prime_UTR_variant	9/9	1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15197 AN: 152010 Hom.: 1069 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0689

Gnomad SAS AF: 0.0833

Gnomad FIN AF: 0.0941

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0547

Gnomad OTH AF: 0.0798

GnomAD4 exome AF: 0.0645 AC: 29727 AN: 460954 Hom.: 1142 Cov.: 5 AF XY: 0.0640 AC XY: 15711 AN XY: 245462

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.0512

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.0618

Gnomad4 SAS exome AF: 0.0669

Gnomad4 FIN exome AF: 0.0847

Gnomad4 NFE exome AF: 0.0549

Gnomad4 OTH exome AF: 0.0716

GnomAD4 genome AF: 0.100 AC: 15219 AN: 152128 Hom.: 1072 Cov.: 33 AF XY: 0.100 AC XY: 7472 AN XY: 74350

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.0622

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0689

Gnomad4 SAS AF: 0.0835

Gnomad4 FIN AF: 0.0941

Gnomad4 NFE AF: 0.0547

Gnomad4 OTH AF: 0.0790

Alfa AF: 0.0662 Hom.: 434

Bravo AF: 0.102

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Ornithine aminotransferase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.58
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs2459216; hg19: chr10-126086326;