rs2459216

Variant names:

• chr10-124397757-G-A
• rs2459216
• NM_000274.4:c.*185C>T

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -2.01
• Publications: 11 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
OAT	NM_000274.4	c.*185C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000368845.6	NP_000265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OAT	ENST00000368845.6	c.*185C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_000274.4	ENSP00000357838.5
OAT	ENST00000539214.5	c.*185C>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000439042.1

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

African (AFR) AF: 0.199 AC: 2478 AN: 12464

American (AMR) AF: 0.0512 AC: 983 AN: 19202

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 1404 AN: 13812

East Asian (EAS) AF: 0.0618 AC: 1828 AN: 29578

South Asian (SAS) AF: 0.0669 AC: 3113 AN: 46528

European-Finnish (FIN) AF: 0.0847 AC: 2328 AN: 27472

Middle Eastern (MID) AF: 0.0723 AC: 139 AN: 1922

European-Non Finnish (NFE) AF: 0.0549 AC: 15594 AN: 284008

Other (OTH) AF: 0.0716 AC: 1860 AN: 25968

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

African (AFR) AF: 0.198 AC: 8213 AN: 41474

American (AMR) AF: 0.0622 AC: 951 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3466

East Asian (EAS) AF: 0.0689 AC: 357 AN: 5184

South Asian (SAS) AF: 0.0835 AC: 402 AN: 4812

European-Finnish (FIN) AF: 0.0941 AC: 994 AN: 10566

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0547 AC: 3720 AN: 68016

Other (OTH) AF: 0.0790 AC: 167 AN: 2114

Alfa AF: 0.0710 Hom.: 693

Bravo AF: 0.102

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ornithine aminotransferase deficiency Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.91
CADD	Benign	0.58
DANN	Benign	0.60
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2459216; hg19: chr10-126086326;