chr11-112025518-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001931.5(DLAT):c.46G>A(p.Ala16Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,614,018 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 19 hom. )
Consequence
DLAT
NM_001931.5 missense
NM_001931.5 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: 0.138
Genes affected
DLAT (HGNC:2896): (dihydrolipoamide S-acetyltransferase) This gene encodes component E2 of the multi-enzyme pyruvate dehydrogenase complex (PDC). PDC resides in the inner mitochondrial membrane and catalyzes the conversion of pyruvate to acetyl coenzyme A. The protein product of this gene, dihydrolipoamide acetyltransferase, accepts acetyl groups formed by the oxidative decarboxylation of pyruvate and transfers them to coenzyme A. Dihydrolipoamide acetyltransferase is the antigen for antimitochondrial antibodies. These autoantibodies are present in nearly 95% of patients with the autoimmune liver disease primary biliary cirrhosis (PBC). In PBC, activated T lymphocytes attack and destroy epithelial cells in the bile duct where this protein is abnormally distributed and overexpressed. PBC enventually leads to cirrhosis and liver failure. Mutations in this gene are also a cause of pyruvate dehydrogenase E2 deficiency which causes primary lactic acidosis in infancy and early childhood.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0025246143).
BP6
?
Variant 11-112025518-G-A is Benign according to our data. Variant chr11-112025518-G-A is described in ClinVar as [Benign]. Clinvar id is 137085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00129 (197/152314) while in subpopulation EAS AF= 0.0308 (159/5158). AF 95% confidence interval is 0.0269. There are 0 homozygotes in gnomad4. There are 118 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DLAT | NM_001931.5 | c.46G>A | p.Ala16Thr | missense_variant | 1/14 | ENST00000280346.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DLAT | ENST00000280346.11 | c.46G>A | p.Ala16Thr | missense_variant | 1/14 | 1 | NM_001931.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00129 AC: 197AN: 152196Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00283 AC: 707AN: 249812Hom.: 7 AF XY: 0.00275 AC XY: 372AN XY: 135326
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GnomAD4 exome AF: 0.00116 AC: 1700AN: 1461704Hom.: 19 Cov.: 30 AF XY: 0.00119 AC XY: 865AN XY: 727166
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GnomAD4 genome ? AF: 0.00129 AC: 197AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.00158 AC XY: 118AN XY: 74478
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 31, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Pyruvate dehydrogenase E2 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 07, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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