Variant rs1799900 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001933.5(DLST):c.1060-29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,607,978 control chromosomes in the GnomAD database, including 262,296 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.65 ( 34054 hom., cov: 33)

Exomes 𝑓: 0.55 ( 228242 hom. )

Consequence

DLST
NM_001933.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.258

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
DLST	NM_001933.5 linkuse as main transcript	c.1060-29G>A	intron_variant	ENST00000334220.9	NP_001924.2
DLST	XM_047431065.1 linkuse as main transcript	c.511-29G>A	intron_variant		XP_047287021.1
DLST	NR_033814.2 linkuse as main transcript	n.1040-29G>A	intron_variant, non_coding_transcript_variant
DLST	NR_045209.2 linkuse as main transcript	n.1049-29G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
DLST	ENST00000334220.9 linkuse as main transcript	c.1060-29G>A	intron_variant	1	NM_001933.5	ENSP00000335304	P1	P36957-1
DLST	ENST00000555089.5 linkuse as main transcript	c.*689-29G>A	intron_variant, NMD_transcript_variant	1		ENSP00000452422
DLST	ENST00000238671.11 linkuse as main transcript	c.*798-29G>A	intron_variant, NMD_transcript_variant	2		ENSP00000238671
DLST	ENST00000554612.5 linkuse as main transcript	c.*803-29G>A	intron_variant, NMD_transcript_variant	2		ENSP00000451670

Frequencies

GnomAD3 genomes

AF:

0.648

AC:

98584

AN:

152052

Hom.:

33999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.907

Gnomad AMI

AF:

0.577

Gnomad AMR

AF:

0.540

Gnomad ASJ

AF:

0.550

Gnomad EAS

AF:

0.448

Gnomad SAS

AF:

0.674

Gnomad FIN

AF:

0.668

Gnomad MID

AF:

0.567

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.617

GnomAD3 exomes

AF:

0.573

AC:

142463

AN:

248454

Hom.:

42586

AF XY:

0.573

AC XY:

76913

AN XY:

134264

show subpopulations

Gnomad AFR exome

AF:

0.916

Gnomad AMR exome

AF:

0.485

Gnomad ASJ exome

AF:

0.537

Gnomad EAS exome

AF:

0.463

Gnomad SAS exome

AF:

0.662

Gnomad FIN exome

AF:

0.653

Gnomad NFE exome

AF:

0.535

Gnomad OTH exome

AF:

0.543

GnomAD4 exome

AF:

0.554

AC:

806428

AN:

1455806

Hom.:

228242

Cov.:

AF XY:

0.556

AC XY:

402937

AN XY:

724232

show subpopulations

Gnomad4 AFR exome

AF:

0.928

Gnomad4 AMR exome

AF:

0.494

Gnomad4 ASJ exome

AF:

0.541

Gnomad4 EAS exome

AF:

0.489

Gnomad4 SAS exome

AF:

0.659

Gnomad4 FIN exome

AF:

0.644

Gnomad4 NFE exome

AF:

0.535

Gnomad4 OTH exome

AF:

0.555

GnomAD4 genome

AF:

0.649

AC:

98695

AN:

152172

Hom.:

34054

Cov.:

AF XY:

0.652

AC XY:

48465

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.907

Gnomad4 AMR

AF:

0.539

Gnomad4 ASJ

AF:

0.550

Gnomad4 EAS

AF:

0.449

Gnomad4 SAS

AF:

0.673

Gnomad4 FIN

AF:

0.668

Gnomad4 NFE

AF:

0.533

Gnomad4 OTH

AF:

0.618

Alfa

AF:

0.568

Hom.:

8107

Bravo

AF:

0.646

Asia WGS

AF:

0.616

AC:

2141

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.4

DANN

Benign

0.72

BranchPoint Hunter

2.0

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