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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAT	NM_000274.4	MANE Select	c.*185C>T		3_prime_UTR	Exon 10 of 10	NP_000265.1
	OAT	NM_001322965.2		c.*185C>T		3_prime_UTR	Exon 10 of 10	NP_001309894.1
	OAT	NM_001322966.2		c.*185C>T		3_prime_UTR	Exon 11 of 11	NP_001309895.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAT	ENST00000368845.6	TSL:1 MANE Select	c.*185C>T		3_prime_UTR	Exon 10 of 10	ENSP00000357838.5
	OAT	ENST00000539214.5	TSL:1	c.*185C>T		3_prime_UTR	Exon 9 of 9	ENSP00000439042.1
	OAT	ENST00000921313.1		c.*185C>T		3_prime_UTR	Exon 10 of 10	ENSP00000591372.1

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Ornithine aminotransferase deficiency (1)

Computational scores

Source: dbNSFP v4.9

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;