rs386833606

Variant names:

• chr10-124408789-ACTC-A
• rs386833606
• NM_000274.4:c.373_375delGAG

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The ENST00000368845.6(OAT):​c.373_375delGAG​(p.Glu125del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: OAT ENST00000368845.6 conservative_inframe_deletion
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.67
• Publications: 1 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in ENST00000368845.6. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 10-124408789-ACTC-A is Pathogenic according to our data. Variant chr10-124408789-ACTC-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 56124.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000368845.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAT	NM_000274.4	MANE Select	c.373_375delGAG	p.Glu125del	conservative_inframe_deletion	Exon 3 of 10	NP_000265.1
	OAT	NM_001322965.2		c.373_375delGAG	p.Glu125del	conservative_inframe_deletion	Exon 3 of 10	NP_001309894.1
	OAT	NM_001322966.2		c.373_375delGAG	p.Glu125del	conservative_inframe_deletion	Exon 4 of 11	NP_001309895.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OAT	ENST00000368845.6	TSL:1 MANE Select	c.373_375delGAG	p.Glu125del	conservative_inframe_deletion	Exon 3 of 10	ENSP00000357838.5
	OAT	ENST00000539214.5	TSL:1	c.-42_-40delGAG		5_prime_UTR	Exon 2 of 9	ENSP00000439042.1
	OAT	ENST00000467675.5	TSL:5	n.-1_2delGAG		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

Significance: Likely pathogenic

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7
Mutation Taster		=8/92	disease causing (ClinVar)

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: rs386833606; hg19: chr10-126097358;