Variant 3-58430811-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000925.4(PDHB):c.435A>G(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 (★★).

Frequency

Genomes: 𝑓 0.98 ( 73904 hom., cov: 32)

Exomes 𝑓: 1.0 ( 728503 hom. )

Consequence

PDHB
NM_000925.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.293

Variant links:

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 links:

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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
PDHB	NM_000925.4 linkuse as main transcript	c.435A>G	p.Arg145=	synonymous_variant	6/10	ENST00000302746.11
PDHB	NM_001315536.2 linkuse as main transcript	c.381A>G	p.Arg127=	synonymous_variant	5/9
PDHB	NM_001173468.2 linkuse as main transcript	c.404-23A>G		intron_variant
PDHB	NR_033384.2 linkuse as main transcript	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 linkuse as main transcript	c.435A>G	p.Arg145=	synonymous_variant	6/10	1	NM_000925.4	P1	P11177-1

Frequencies

GnomAD3 genomes

AF:

0.985

AC:

149894

AN:

152204

Hom.:

73848

Cov.:

show subpopulations

Gnomad AFR

AF:

0.948

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.994

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.991

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.985

GnomAD3 exomes

AF:

0.996

AC:

250445

AN:

251488

Hom.:

124731

AF XY:

0.997

AC XY:

135510

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.947

Gnomad AMR exome

AF:

0.997

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.998

GnomAD4 exome

AF:

0.998

AC:

1459397

AN:

1461874

Hom.:

728503

Cov.:

AF XY:

0.999

AC XY:

726176

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.949

Gnomad4 AMR exome

AF:

0.997

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.996

GnomAD4 genome

AF:

0.985

AC:

150009

AN:

152322

Hom.:

73904

Cov.:

AF XY:

0.986

AC XY:

73424

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.948

Gnomad4 AMR

AF:

0.994

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.985

Alfa

AF:

0.992

Hom.:

39112

Bravo

AF:

0.983

Asia WGS

AF:

0.998

AC:

3469

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

1.00

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.84

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over