chr10-124412119-A-ACTCC

Variant names:

• chr10-124412119-A-ACTCC
• rs1554867854
• NM_000274.4:c.49_52dupGGAG

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000274.4(OAT):​c.49_52dupGGAG​(p.Val18GlyfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OAT NM_000274.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: -0.561
• Publications: 0 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: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 123 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-124412119-A-ACTCC is Pathogenic according to our data. Variant chr10-124412119-A-ACTCC is described in ClinVar as Pathogenic. ClinVar VariationId is 456522.Status of the report is criteria_provided_single_submitter, 1 stars.

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.49_52dupGGAG	p.Val18GlyfsTer15	frameshift	Exon 2 of 10	NP_000265.1	P04181-1
	OAT	NM_001322965.2		c.49_52dupGGAG	p.Val18GlyfsTer15	frameshift	Exon 2 of 10	NP_001309894.1	P04181-1
	OAT	NM_001322966.2		c.49_52dupGGAG	p.Val18GlyfsTer15	frameshift	Exon 3 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.49_52dupGGAG	p.Val18GlyfsTer15	frameshift	Exon 2 of 10	ENSP00000357838.5	P04181-1
	OAT	ENST00000539214.5	TSL:1	c.-215-3158_-215-3155dupGGAG		intron	N/A	ENSP00000439042.1	P04181-2
	OAT	ENST00000921313.1		c.49_52dupGGAG	p.Val18GlyfsTer15	frameshift	Exon 2 of 10	ENSP00000591372.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Ornithine aminotransferase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.56
Mutation Taster		=0/200	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs1554867854; hg19: chr10-126100688;