rs732765

chr14-74899026-A-G

Variant summary

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

The NM_001933.5(DLST):c.901+527A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,992 control chromosomes in the GnomAD database, including 9,256 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 0.32 (9256 hom., cov: 32)
• Consequence: DLST NM_001933.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409

Genes affected

DLST (HGNC:2911): (dihydrolipoamide S-succinyltransferase) This gene encodes a mitochondrial protein that belongs to the 2-oxoacid dehydrogenase family. This protein is one of the three components (the E2 component) of the 2-oxoglutarate dehydrogenase complex that catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLST	NM_001933.5	c.901+527A>G		intron_variant		ENST00000334220.9
DLST	XM_047431065.1	c.352+527A>G		intron_variant
DLST	NR_033814.2	n.881+527A>G		intron_variant, non_coding_transcript_variant
DLST	NR_045209.2	n.890+527A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLST	ENST00000334220.9	c.901+527A>G		intron_variant		1	NM_001933.5	P1
DLST	ENST00000555089.5	c.*530+527A>G		intron_variant, NMD_transcript_variant		1
DLST	ENST00000238671.11	c.*639+527A>G		intron_variant, NMD_transcript_variant		2
DLST	ENST00000554612.5	c.*644+527A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48486 AN: 151874 Hom.: 9234 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.287

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.319 AC: 48560 AN: 151992 Hom.: 9256 Cov.: 32 AF XY: 0.322 AC XY: 23883 AN XY: 74244

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.283

Alfa AF: 0.251 Hom.: 3599

Bravo AF: 0.324

Asia WGS AF: 0.315 AC: 1096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.9
Dann	Benign	0.41

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: rs732765; hg19: chr14-75365729;