rs9371

chr11-112062954-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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]

PIH1D2 (HGNC:):

ACMG classification

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/exons	MANE	UniProt
DLAT	NM_001931.5	c.*419A>G		3_prime_UTR_variant	14/14	ENST00000280346.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLAT	ENST00000280346.11	c.*419A>G		3_prime_UTR_variant	14/14	1	NM_001931.5	P3

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76813 AN: 151930 Hom.: 21714 Cov.: 32

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.: 0 AF XY: 0.404 AC XY: 2859 AN XY: 7082

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.: 32 AF XY: 0.509 AC XY: 37838 AN XY: 74288

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

Other links and lift over

dbSNP: rs9371; hg19: chr11-111933678;