Genetic Variant NM_001931.5:c.*419A>G (chr11-112062954-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001931.5(DLAT):c.*419A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 165,156 control chromosomes in the GnomAD database, including 22,935 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 0.51 ( 21768 hom., cov: 32)

Exomes 𝑓: 0.40 ( 1167 hom. )

Consequence

DLAT
NM_001931.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0980

Variant links:

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]

DLAT links:

PIH1D2 (HGNC:25210): (PIH1 domain containing 2) Enables small GTPase binding activity. Predicted to be involved in box C/D snoRNP assembly and rRNA processing. Predicted to be part of R2TP complex and ribonucleoprotein complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PIH1D2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLAT	NM_001931.5 link	c.*419A>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000280346.11	NP_001922.2	P10515Q86YI5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLAT	ENST00000280346.11 link	c.*419A>G		3_prime_UTR_variant	Exon 14 of 14	1	NM_001931.5	ENSP00000280346.7		P10515

Frequencies

GnomAD3 genomes

AF:

0.506

AC:

76813

AN:

151930

Hom.:

21714

Cov.:

show subpopulations

Gnomad AFR

AF:

0.777

Gnomad AMI

AF:

0.548

Gnomad AMR

AF:

0.421

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.583

Gnomad SAS

AF:

0.419

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.381

Gnomad OTH

AF:

0.447

GnomAD4 exome

AF:

0.400

AC:

5240

AN:

13108

Hom.:

1167

Cov.:

AF XY:

0.404

AC XY:

2859

AN XY:

7082

show subpopulations

Gnomad4 AFR exome

AF:

0.770

Gnomad4 AMR exome

AF:

0.431

Gnomad4 ASJ exome

AF:

0.323

Gnomad4 EAS exome

AF:

0.549

Gnomad4 SAS exome

AF:

0.424

Gnomad4 FIN exome

AF:

0.359

Gnomad4 NFE exome

AF:

0.367

Gnomad4 OTH exome

AF:

0.387

GnomAD4 genome

AF:

0.506

AC:

76925

AN:

152048

Hom.:

21768

Cov.:

AF XY:

0.509

AC XY:

37838

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.777

Gnomad4 AMR

AF:

0.421

Gnomad4 ASJ

AF:

0.301

Gnomad4 EAS

AF:

0.583

Gnomad4 SAS

AF:

0.418

Gnomad4 FIN

AF:

0.447

Gnomad4 NFE

AF:

0.381

Gnomad4 OTH

AF:

0.447

Alfa

AF:

0.432

Hom.:

3949

Bravo

AF:

0.520

Asia WGS

AF:

0.480

AC:

1671

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.7

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over