10-124397407-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000274.4(OAT):c.*535T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0639 in 152,442 control chromosomes in the GnomAD database, including 433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.064 (433 hom., cov: 33)
  • Exomes 𝑓: 0.046 (0 hom.)
• Consequence: OAT NM_000274.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.87

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-124397407-A-G is Benign according to our data. Variant chr10-124397407-A-G is described in ClinVar as [Benign]. Clinvar id is 299162.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OAT	NM_000274.4	c.*535T>C		3_prime_UTR_variant	10/10	ENST00000368845.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OAT	ENST00000368845.6	c.*535T>C		3_prime_UTR_variant	10/10	1	NM_000274.4	P1
OAT	ENST00000539214.5	c.*535T>C		3_prime_UTR_variant	9/9	1

Frequencies

GnomAD3 genomes AF: 0.0640 AC: 9736 AN: 152194 Hom.: 433 Cov.: 33

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0414

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.0550

Gnomad SAS AF: 0.0637

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0844

Gnomad OTH AF: 0.0463

GnomAD4 exome AF: 0.0462 AC: 6 AN: 130 Hom.: 0 Cov.: 0 AF XY: 0.0500 AC XY: 3 AN XY: 60

Gnomad4 AMR exome AF: 0.0625

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0463

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0639 AC: 9740 AN: 152312 Hom.: 433 Cov.: 33 AF XY: 0.0661 AC XY: 4925 AN XY: 74472

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.0415

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.0551

Gnomad4 SAS AF: 0.0642

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.0844

Gnomad4 OTH AF: 0.0458

Alfa AF: 0.0800 Hom.: 81

Bravo AF: 0.0510

Asia WGS AF: 0.0500 AC: 174 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ornithine aminotransferase deficiency Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	9.2
Dann	Benign	0.87

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: rs8182; hg19: chr10-126085976;