rs386833611

Variant names:

• chr10-124408575-TGCCCTTCACGGTATA-T
• rs386833611
• NM_000274.4:c.472_486delTATACCGTGAAGGGC

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM1 PM4 PP3 PP5_Moderate

The NM_000274.4(OAT):​c.472_486delTATACCGTGAAGGGC​(p.Tyr158_Gly162del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: OAT NM_000274.4 conservative_inframe_deletion
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 7.66
• 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: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

• PM1: In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 6 uncertain in NM_000274.4
• PM4: Nonframeshift variant in NON repetitive region in NM_000274.4.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 10-124408575-TGCCCTTCACGGTATA-T is Pathogenic according to our data. Variant chr10-124408575-TGCCCTTCACGGTATA-T is described in ClinVar as Pathogenic. ClinVar VariationId is 56129.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.472_486delTATACCGTGAAGGGC	p.Tyr158_Gly162del	conservative_inframe_deletion	Exon 4 of 10	NP_000265.1	P04181-1
	OAT	NM_001322965.2		c.472_486delTATACCGTGAAGGGC	p.Tyr158_Gly162del	conservative_inframe_deletion	Exon 4 of 10	NP_001309894.1	P04181-1
	OAT	NM_001322966.2		c.472_486delTATACCGTGAAGGGC	p.Tyr158_Gly162del	conservative_inframe_deletion	Exon 5 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.472_486delTATACCGTGAAGGGC	p.Tyr158_Gly162del	conservative_inframe_deletion	Exon 4 of 10	ENSP00000357838.5	P04181-1
	OAT	ENST00000539214.5	TSL:1	c.58_72delTATACCGTGAAGGGC	p.Tyr20_Gly24del	conservative_inframe_deletion	Exon 3 of 9	ENSP00000439042.1	P04181-2
	OAT	ENST00000921313.1		c.472_486delTATACCGTGAAGGGC	p.Tyr158_Gly162del	conservative_inframe_deletion	Exon 4 of 10	ENSP00000591372.1

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

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
2	-	-	Ornithine aminotransferase deficiency (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7
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: rs386833611; hg19: chr10-126097144;