rs386833609

Positions:

• chr10-124408632-CCACTCCTAT-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_000274.4(OAT):​c.425-4_429delATAGGAGTG​(p.Val143fs) variant causes a frameshift, splice acceptor, splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,412 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: OAT NM_000274.4 frameshift, splice_acceptor, splice_region, intron
• Clinical Significance: Pathogenic/Likely pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 8.94

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 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-124408632-CCACTCCTAT-C is Pathogenic according to our data. Variant chr10-124408632-CCACTCCTAT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 165.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-124408632-CCACTCCTAT-C is described in Lovd as [Likely_pathogenic]. Variant chr10-124408632-CCACTCCTAT-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OAT	NM_000274.4	c.425-4_429delATAGGAGTG	p.Val143fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	4/10	ENST00000368845.6	NP_000265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OAT	ENST00000368845.6	c.425-4_429delATAGGAGTG	p.Val143fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	4/10	1	NM_000274.4	ENSP00000357838.5
OAT	ENST00000539214.5	c.11-4_15delATAGGAGTG	p.Val5fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	3/9	1		ENSP00000439042.1
OAT	ENST00000467675.5	n.52-4_56delATAGGAGTG		splice_acceptor_variant, splice_region_variant, intron_variant, non_coding_transcript_exon_variant	2/7	5
OAT	ENST00000476917.5	n.490-4_494delATAGGAGTG		splice_acceptor_variant, splice_region_variant, intron_variant, non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251254 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135862

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1458412 Hom.: 0 AF XY: 0.00000413 AC XY: 3 AN XY: 725746

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000451

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Ornithine aminotransferase deficiency Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Nov 01, 1990	- -
Likely pathogenic, no assertion criteria provided	literature only	Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	-	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs386833609; hg19: chr10-126097201;