rs731952

Positions:

• chr14-74899744-C-T

Variant summary

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

The NM_001933.5(DLST):​c.902-179C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 151,948 control chromosomes in the GnomAD database, including 7,721 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 (7721 hom., cov: 31)
• Consequence: DLST NM_001933.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648

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]

DLST (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLST	NM_001933.5	c.902-179C>T		intron_variant		ENST00000334220.9	NP_001924.2
DLST	XM_047431065.1	c.353-179C>T		intron_variant			XP_047287021.1
DLST	NR_033814.2	n.882-179C>T		intron_variant
DLST	NR_045209.2	n.891-179C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLST	ENST00000334220.9	c.902-179C>T		intron_variant		1	NM_001933.5	ENSP00000335304.4
DLST	ENST00000555089.5	n.*531-179C>T		intron_variant		1		ENSP00000452422.1
DLST	ENST00000238671.11	n.*640-179C>T		intron_variant		2		ENSP00000238671.7
DLST	ENST00000554612.5	n.*645-179C>T		intron_variant		2		ENSP00000451670.1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47867 AN: 151830 Hom.: 7712 Cov.: 31

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.315 AC: 47891 AN: 151948 Hom.: 7721 Cov.: 31 AF XY: 0.316 AC XY: 23489 AN XY: 74262

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.323

Alfa AF: 0.307 Hom.: 1537

Bravo AF: 0.307

Asia WGS AF: 0.298 AC: 1034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.30
DANN	Benign	0.35

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: rs731952; hg19: chr14-75366447; COSMIC: COSV53167862; COSMIC: COSV53167862;