X-24465305-T-TGCTGCTGCGGCTGCTGCG

Variant names:

• chrX-24465305-T-TGCTGCTGCGGCTGCTGCG
• rs764167975
• NM_005391.5:c.-140_-139insTGCTGCGGCTGCTGCGGC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005391.5(PDK3):​c.-140_-139insTGCTGCGGCTGCTGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000417 in 239,532 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000042 (0 hom. 0 hem.)
• Consequence: PDK3 NM_005391.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDK3	NM_005391.5	c.-140_-139insTGCTGCGGCTGCTGCGGC		5_prime_UTR_variant	Exon 1 of 11	ENST00000379162.9	NP_005382.1
PDK3	NM_001142386.3	c.-140_-139insTGCTGCGGCTGCTGCGGC		5_prime_UTR_variant	Exon 1 of 12		NP_001135858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDK3	ENST00000379162	c.-140_-139insTGCTGCGGCTGCTGCGGC		5_prime_UTR_variant	Exon 1 of 11	1	NM_005391.5	ENSP00000368460.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000417 AC: 1 AN: 239532 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 75244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000640

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs764167975; hg19: chrX-24483422;