Variant X-24465491-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_005391.5(PDK3):c.36G>A(p.Val12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000993 in 1,209,010 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 3 hem., cov: 25)

Exomes 𝑓: 0.000097 ( 0 hom. 37 hem. )

Consequence

PDK3
NM_005391.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0370

Variant links:

Genes affected

PDK3 (HGNC:8811): (pyruvate dehydrogenase kinase 3) The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2). It provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle, and thus is one of the major enzymes responsible for the regulation of glucose metabolism. The enzymatic activity of PDH is regulated by a phosphorylation/dephosphorylation cycle, and phosphorylation results in inactivation of PDH. The protein encoded by this gene is one of the three pyruvate dehydrogenase kinases that inhibits the PDH complex by phosphorylation of the E1 alpha subunit. This gene is predominantly expressed in the heart and skeletal muscles. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

PDK3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant X-24465491-G-A is Benign according to our data. Variant chrX-24465491-G-A is described in ClinVar as [Benign]. Clinvar id is 1167761.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-24465491-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.037 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDK3	NM_005391.5 linkuse as main transcript	c.36G>A	p.Val12=	synonymous_variant	1/11	ENST00000379162.9
PDK3	NM_001142386.3 linkuse as main transcript	c.36G>A	p.Val12=	synonymous_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDK3	ENST00000379162.9 linkuse as main transcript	c.36G>A	p.Val12=	synonymous_variant	1/11	1	NM_005391.5	P1	Q15120-1
PDK3	ENST00000568479.2 linkuse as main transcript	c.36G>A	p.Val12=	synonymous_variant	1/12				Q15120-2
PDK3	ENST00000493226.2 linkuse as main transcript	n.248G>A		non_coding_transcript_exon_variant	1/3	5
PDK3	ENST00000648777.1 linkuse as main transcript	c.36G>A	p.Val12=	synonymous_variant, NMD_transcript_variant	1/12				Q15120-1

Frequencies

GnomAD3 genomes

AF:

0.000123

AC:

AN:

113383

Hom.:

Cov.:

AF XY:

0.0000844

AC XY:

AN XY:

35527

show subpopulations

Gnomad AFR

AF:

0.0000319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000158

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000225

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000860

AC:

AN:

174405

Hom.:

AF XY:

0.0000793

AC XY:

AN XY:

63077

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000107

Gnomad FIN exome

AF:

0.0000647

Gnomad NFE exome

AF:

0.000157

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000967

AC:

106

AN:

1095627

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

361529

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000555

Gnomad4 FIN exome

AF:

0.0000250

Gnomad4 NFE exome

AF:

0.000117

Gnomad4 OTH exome

AF:

0.0000653

GnomAD4 genome

AF:

0.000123

AC:

AN:

113383

Hom.:

Cov.:

AF XY:

0.0000844

AC XY:

AN XY:

35527

show subpopulations

Gnomad4 AFR

AF:

0.0000319

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000158

Gnomad4 NFE

AF:

0.000225

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000831

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease X-linked dominant 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.98

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