rs911
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_018444.4(PDP1):c.*631G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 166,862 control chromosomes in the GnomAD database, including 23,486 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.52 ( 22124 hom., cov: 33)
Exomes 𝑓: 0.43 ( 1362 hom. )
Consequence
PDP1
NM_018444.4 3_prime_UTR
NM_018444.4 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.39
Genes affected
PDP1 (HGNC:9279): (pyruvate dehydrogenase phosphatase catalytic subunit 1) Pyruvate dehydrogenase (E1) is one of the three components (E1, E2, and E3) of the large pyruvate dehydrogenase complex. Pyruvate dehydrogenase kinases catalyze phosphorylation of serine residues of E1 to inactivate the E1 component and inhibit the complex. Pyruvate dehydrogenase phosphatases catalyze the dephosphorylation and activation of the E1 component to reverse the effects of pyruvate dehydrogenase kinases. Pyruvate dehydrogenase phosphatase is a heterodimer consisting of catalytic and regulatory subunits. Two catalytic subunits have been reported; one is predominantly expressed in skeletal muscle and another one is is much more abundant in the liver. The catalytic subunit, encoded by this gene, is the former, and belongs to the protein phosphatase 2C (PP2C) superfamily. Along with the pyruvate dehydrogenase complex and pyruvate dehydrogenase kinases, this enzyme is located in the mitochondrial matrix. Mutation in this gene causes pyruvate dehydrogenase phosphatase deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Jun 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDP1 | NM_018444.4 | c.*631G>C | 3_prime_UTR_variant | 2/2 | ENST00000297598.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDP1 | ENST00000297598.5 | c.*631G>C | 3_prime_UTR_variant | 2/2 | 1 | NM_018444.4 | P4 | ||
PDP1 | ENST00000520728.5 | c.*631G>C | 3_prime_UTR_variant | 3/3 | 1 | P4 | |||
PDP1 | ENST00000396200.3 | c.*631G>C | 3_prime_UTR_variant | 3/3 | 4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.523 AC: 79411AN: 151978Hom.: 22069 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
79411
AN:
151978
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.428 AC: 6315AN: 14766Hom.: 1362 Cov.: 0 AF XY: 0.424 AC XY: 2978AN XY: 7024
GnomAD4 exome
AF:
AC:
6315
AN:
14766
Hom.:
Cov.:
0
AF XY:
AC XY:
2978
AN XY:
7024
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.523 AC: 79530AN: 152096Hom.: 22124 Cov.: 33 AF XY: 0.526 AC XY: 39099AN XY: 74346
GnomAD4 genome
?
AF:
AC:
79530
AN:
152096
Hom.:
Cov.:
33
AF XY:
AC XY:
39099
AN XY:
74346
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at