rs11461

Variant names:

• chr10-124400865-G-A
• rs11461
• NM_000274.4:c.1134C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.1134C>T	p.Asn378Asn	synonymous	Exon 9 of 10	NP_000265.1	P04181-1
	OAT	NM_001322965.2		c.1134C>T	p.Asn378Asn	synonymous	Exon 9 of 10	NP_001309894.1	P04181-1
	OAT	NM_001322966.2		c.1134C>T	p.Asn378Asn	synonymous	Exon 10 of 11	NP_001309895.1	P04181-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAT	ENST00000368845.6	TSL:1 MANE Select	c.1134C>T	p.Asn378Asn	synonymous	Exon 9 of 10	ENSP00000357838.5	P04181-1
	OAT	ENST00000539214.5	TSL:1	c.720C>T	p.Asn240Asn	synonymous	Exon 8 of 9	ENSP00000439042.1	P04181-2
	OAT	ENST00000921313.1		c.1137C>T	p.Asn379Asn	synonymous	Exon 9 of 10	ENSP00000591372.1

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

GnomAD2 exomes AF: 0.428 AC: 106738 AN: 249636 AF XY: 0.428

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 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

African (AFR) AF: 0.154 AC: 5121 AN: 33200

American (AMR) AF: 0.577 AC: 25701 AN: 44524

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 11357 AN: 25958

East Asian (EAS) AF: 0.616 AC: 24310 AN: 39474

South Asian (SAS) AF: 0.476 AC: 40681 AN: 85488

European-Finnish (FIN) AF: 0.376 AC: 20048 AN: 53342

Middle Eastern (MID) AF: 0.411 AC: 1692 AN: 4112

European-Non Finnish (NFE) AF: 0.378 AC: 413092 AN: 1093676

Other (OTH) AF: 0.398 AC: 23652 AN: 59496

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

African (AFR) AF: 0.166 AC: 6865 AN: 41470

American (AMR) AF: 0.480 AC: 7333 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1530 AN: 3470

East Asian (EAS) AF: 0.618 AC: 3195 AN: 5172

South Asian (SAS) AF: 0.482 AC: 2327 AN: 4826

European-Finnish (FIN) AF: 0.366 AC: 3862 AN: 10550

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26585 AN: 67988

Other (OTH) AF: 0.371 AC: 782 AN: 2108

Alfa AF: 0.380 Hom.: 9721

Bravo AF: 0.346

Asia WGS AF: 0.522 AC: 1811 AN: 3478

EpiCase AF: 0.394

EpiControl AF: 0.383

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	Ornithine aminotransferase deficiency (6)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.77
DANN	Benign	0.58
PhyloP100		-0.087
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

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