chr3-58430811-T-C
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000925.4(PDHB):āc.435A>Gā(p.Arg145=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 1,614,196 control chromosomes in the GnomAD database, including 802,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.98 ( 73904 hom., cov: 32)
Exomes š: 1.0 ( 728503 hom. )
Consequence
PDHB
NM_000925.4 synonymous
NM_000925.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.293
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 3-58430811-T-C is Benign according to our data. Variant chr3-58430811-T-C is described in ClinVar as [Benign]. Clinvar id is 559256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-58430811-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.293 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDHB | NM_000925.4 | c.435A>G | p.Arg145= | synonymous_variant | 6/10 | ENST00000302746.11 | |
PDHB | NM_001315536.2 | c.381A>G | p.Arg127= | synonymous_variant | 5/9 | ||
PDHB | NM_001173468.2 | c.404-23A>G | intron_variant | ||||
PDHB | NR_033384.2 | n.541A>G | non_coding_transcript_exon_variant | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDHB | ENST00000302746.11 | c.435A>G | p.Arg145= | synonymous_variant | 6/10 | 1 | NM_000925.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.985 AC: 149894AN: 152204Hom.: 73848 Cov.: 32
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GnomAD3 exomes AF: 0.996 AC: 250445AN: 251488Hom.: 124731 AF XY: 0.997 AC XY: 135510AN XY: 135918
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GnomAD4 exome AF: 0.998 AC: 1459397AN: 1461874Hom.: 728503 Cov.: 54 AF XY: 0.999 AC XY: 726176AN XY: 727238
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GnomAD4 genome AF: 0.985 AC: 150009AN: 152322Hom.: 73904 Cov.: 32 AF XY: 0.986 AC XY: 73424AN XY: 74486
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Pyruvate dehydrogenase E1-beta deficiency Benign:3
Benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | Jun 15, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 23, 2016 | - - |
Pyruvate dehydrogenase phosphatase deficiency Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 16, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at