NM_000925.4:c.*160A>G

Variant names:

• chr3-58427874-T-C
• rs2062883381
• NM_000925.4:c.*160A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000925.4(PDHB):​c.*160A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDHB NM_000925.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.506
• 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: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.*160A>G		3_prime_UTR	Exon 10 of 10	NP_000916.2	A0A384MDR8
	PDHB	NM_001173468.2		c.*160A>G		3_prime_UTR	Exon 11 of 11	NP_001166939.1	P11177-3
	PDHB	NM_001315536.2		c.*160A>G		3_prime_UTR	Exon 9 of 9	NP_001302465.1	P11177-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDHB	ENST00000302746.11	TSL:1 MANE Select	c.*160A>G		3_prime_UTR	Exon 10 of 10	ENSP00000307241.6	P11177-1
	PDHB	ENST00000383714.8	TSL:1	c.*160A>G		3_prime_UTR	Exon 9 of 9	ENSP00000373220.4	P11177-2
	PDHB	ENST00000461692.5	TSL:1	n.1353A>G		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 5

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Pyruvate dehydrogenase E1-beta deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.55
PhyloP100		-0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2062883381; hg19: chr3-58413601;