rs1554572756

chr8-93922908-CCTT-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM4_Supporting PP5

The NM_018444.4(PDP1):c.851_853del(p.Leu284del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDP1 NM_018444.4 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.97

Genes affected

PDP1 (HGNC:9279): (pyruvate dehydrogenase phosphatase catalytic subunit 1) Pyruvate dehydrogenase (E1) is one of the three components (E1, E2, and E3) of the large pyruvate dehydrogenase complex. Pyruvate dehydrogenase kinases catalyze phosphorylation of serine residues of E1 to inactivate the E1 component and inhibit the complex. Pyruvate dehydrogenase phosphatases catalyze the dephosphorylation and activation of the E1 component to reverse the effects of pyruvate dehydrogenase kinases. Pyruvate dehydrogenase phosphatase is a heterodimer consisting of catalytic and regulatory subunits. Two catalytic subunits have been reported; one is predominantly expressed in skeletal muscle and another one is is much more abundant in the liver. The catalytic subunit, encoded by this gene, is the former, and belongs to the protein phosphatase 2C (PP2C) superfamily. Along with the pyruvate dehydrogenase complex and pyruvate dehydrogenase kinases, this enzyme is located in the mitochondrial matrix. Mutation in this gene causes pyruvate dehydrogenase phosphatase deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_018444.4. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 8-93922908-CCTT-C is Pathogenic according to our data. Variant chr8-93922908-CCTT-C is described in ClinVar as [Pathogenic]. Clinvar id is 4663.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDP1	NM_018444.4	c.851_853del	p.Leu284del	inframe_deletion	2/2	ENST00000297598.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDP1	ENST00000297598.5	c.851_853del	p.Leu284del	inframe_deletion	2/2	1	NM_018444.4	P4
PDP1	ENST00000520728.5	c.851_853del	p.Leu284del	inframe_deletion	3/3	1		P4
PDP1	ENST00000396200.3	c.926_928del	p.Leu309del	inframe_deletion	3/3	4		A1
PDP1	ENST00000517764.1	c.851_853del	p.Leu284del	inframe_deletion	2/2	2		P4

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Pyruvate dehydrogenase phosphatase deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 2005

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554572756; hg19: chr8-94935136;