PDHB p.Arg145Arg

Variant names:

• chr3-58430810-C-C
• NM_000925.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr3-58430811--
• chr3-58430813-T-G
• chr3-58430811-T-C
• chr3-58430811-TCT-ACG
• chr3-58430811-TCT-GCG
• chr3-58430811-TCT-CCG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000925.4(PDHB):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDHB NM_000925.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 0 publications found

Genes affected

PDHB (HGNC:8808): (pyruvate dehydrogenase E1 subunit beta) The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and carbon dioxide, and provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle. The PDH complex is composed of multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3). The E1 enzyme is a heterotetramer of two alpha and two beta subunits. This gene encodes the E1 beta subunit. Mutations in this gene are associated with pyruvate dehydrogenase E1-beta deficiency. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2012]

PDHB Gene-Disease associations (from GenCC):

• pyruvate dehydrogenase E1-beta deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000925.4. 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
	PDHB	NM_000925.4	MANE Select	c.		exon_region	Exon 6 of 10	NP_000916.2	A0A384MDR8
	PDHB	NM_001315536.2		c.		exon_region	Exon 5 of 9	NP_001302465.1	P11177-2
	PDHB	NM_001173468.2		c.		intron	N/A	NP_001166939.1	P11177-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDHB	ENST00000302746.11	TSL:1 MANE Select	c.		exon_region	Exon 6 of 10	ENSP00000307241.6	P11177-1
	PDHB	ENST00000383714.8	TSL:1	c.		exon_region	Exon 5 of 9	ENSP00000373220.4	P11177-2
	PDHB	ENST00000461692.5	TSL:1	n.		exon_region	Exon 5 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.29

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-58416537;