11-112025712-G-A
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001931.5(DLAT):c.240G>A(p.Ser80=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,612,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
DLAT
NM_001931.5 synonymous
NM_001931.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.327
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 -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 11-112025712-G-A is Benign according to our data. Variant chr11-112025712-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 507544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.327 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DLAT | NM_001931.5 | c.240G>A | p.Ser80= | synonymous_variant | 1/14 | ENST00000280346.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DLAT | ENST00000280346.11 | c.240G>A | p.Ser80= | synonymous_variant | 1/14 | 1 | NM_001931.5 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000491 AC: 12AN: 244474Hom.: 0 AF XY: 0.0000673 AC XY: 9AN XY: 133650
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GnomAD4 exome AF: 0.0000233 AC: 34AN: 1460488Hom.: 0 Cov.: 34 AF XY: 0.0000248 AC XY: 18AN XY: 726532
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152290Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74464
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 28, 2017 | 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
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 14, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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