14-74889971-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001933.5(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 NM_001933.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.924

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 -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 GnomAd at 1408 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLST	NM_001933.5	c.330+19C>T		intron_variant		ENST00000334220.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLST	ENST00000334220.9	c.330+19C>T		intron_variant		1	NM_001933.5	P1

Frequencies

GnomAD3 genomes AF: 0.00926 AC: 1408 AN: 151986 Hom.: 16 Cov.: 31

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.: 47 AF XY: 0.0137 AC XY: 1841 AN XY: 134684

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.: 29 AF XY: 0.0115 AC XY: 8374 AN XY: 725458

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.: 17 Cov.: 31 AF XY: 0.00969 AC XY: 720 AN XY: 74338

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.: 1

Bravo AF: 0.00882

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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

Other links and lift over

dbSNP: rs111855284; hg19: chr14-75356674; COSMIC: COSV53167425; COSMIC: COSV53167425;