Variant 14-74889971-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000334220.9(DLST):c.330+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,610,318 control chromosomes in the GnomAD database, including 202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0093 ( 17 hom., cov: 31)

Exomes 𝑓: 0.011 ( 185 hom. )

Consequence

DLST
ENST00000334220.9 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.924

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 -14 ACMG points.

BP4

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

BP6

Variant 14-74889971-C-T is Benign according to our data. Variant chr14-74889971-C-T is described in ClinVar as [Benign]. Clinvar id is 2798137.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00934 (1420/152098) while in subpopulation SAS AF= 0.0407 (196/4820). AF 95% confidence interval is 0.036. There are 17 homozygotes in gnomad4. There are 720 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1420 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLST	NM_001933.5 linkuse as main transcript	c.330+19C>T		intron_variant		ENST00000334220.9	NP_001924.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLST	ENST00000334220.9 linkuse as main transcript	c.330+19C>T		intron_variant		1	NM_001933.5	ENSP00000335304	P1	P36957-1

Frequencies

GnomAD3 genomes

AF:

0.00926

AC:

1408

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00418

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.00983

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.00926

Gnomad SAS

AF:

0.0406

Gnomad FIN

AF:

0.00303

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0121

AC:

3020

AN:

249114

Hom.:

AF XY:

0.0137

AC XY:

1841

AN XY:

134684

show subpopulations

Gnomad AFR exome

AF:

0.00385

Gnomad AMR exome

AF:

0.00739

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.00952

Gnomad SAS exome

AF:

0.0388

Gnomad FIN exome

AF:

0.00278

Gnomad NFE exome

AF:

0.00982

Gnomad OTH exome

AF:

0.0136

GnomAD4 exome

AF:

0.0106

AC:

15422

AN:

1458220

Hom.:

185

Cov.:

AF XY:

0.0115

AC XY:

8374

AN XY:

725458

show subpopulations

Gnomad4 AFR exome

AF:

0.00468

Gnomad4 AMR exome

AF:

0.00770

Gnomad4 ASJ exome

AF:

0.0110

Gnomad4 EAS exome

AF:

0.0141

Gnomad4 SAS exome

AF:

0.0385

Gnomad4 FIN exome

AF:

0.00319

Gnomad4 NFE exome

AF:

0.00876

Gnomad4 OTH exome

AF:

0.0119

GnomAD4 genome

AF:

0.00934

AC:

1420

AN:

152098

Hom.:

Cov.:

AF XY:

0.00969

AC XY:

720

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00443

Gnomad4 AMR

AF:

0.00982

Gnomad4 ASJ

AF:

0.00950

Gnomad4 EAS

AF:

0.00948

Gnomad4 SAS

AF:

0.0407

Gnomad4 FIN

AF:

0.00303

Gnomad4 NFE

AF:

0.0103

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00609

Hom.:

Bravo

AF:

0.00882

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.070

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over