14-74889367-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001933.5(DLST):c.274+18A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (2 hom., cov: 17)
  • Exomes 𝑓: 0.0078 (23 hom.)
• Consequence: DLST NM_001933.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.15

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-74889367-A-T is Benign according to our data. Variant chr14-74889367-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2814805.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 668 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLST	NM_001933.5	c.274+18A>T		intron_variant		ENST00000334220.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLST	ENST00000334220.9	c.274+18A>T		intron_variant		1	NM_001933.5	P1

Frequencies

GnomAD3 genomes AF: 0.00551 AC: 668 AN: 121328 Hom.: 2 Cov.: 17

Gnomad AFR AF: 0.00400

Gnomad AMI AF: 0.00242

Gnomad AMR AF: 0.00271

Gnomad ASJ AF: 0.00223

Gnomad EAS AF: 0.000935

Gnomad SAS AF: 0.00342

Gnomad FIN AF: 0.00446

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00765

Gnomad OTH AF: 0.00491

GnomAD3 exomes AF: 0.0687 AC: 5139 AN: 74846 Hom.: 4 AF XY: 0.0751 AC XY: 2986 AN XY: 39736

Gnomad AFR exome AF: 0.0669

Gnomad AMR exome AF: 0.0255

Gnomad ASJ exome AF: 0.0682

Gnomad EAS exome AF: 0.0180

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.0674

Gnomad OTH exome AF: 0.0440

GnomAD4 exome AF: 0.00778 AC: 8470 AN: 1088124 Hom.: 23 Cov.: 17 AF XY: 0.00819 AC XY: 4455 AN XY: 543984

Gnomad4 AFR exome AF: 0.00444

Gnomad4 AMR exome AF: 0.00887

Gnomad4 ASJ exome AF: 0.00736

Gnomad4 EAS exome AF: 0.00158

Gnomad4 SAS exome AF: 0.0129

Gnomad4 FIN exome AF: 0.0161

Gnomad4 NFE exome AF: 0.00753

Gnomad4 OTH exome AF: 0.00528

GnomAD4 genome AF: 0.00551 AC: 669 AN: 121308 Hom.: 2 Cov.: 17 AF XY: 0.00565 AC XY: 321 AN XY: 56766

Gnomad4 AFR AF: 0.00399

Gnomad4 AMR AF: 0.00271

Gnomad4 ASJ AF: 0.00223

Gnomad4 EAS AF: 0.000939

Gnomad4 SAS AF: 0.00371

Gnomad4 FIN AF: 0.00446

Gnomad4 NFE AF: 0.00765

Gnomad4 OTH AF: 0.00489

Alfa AF: 0.00743 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.55
Dann	Benign	0.50

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: rs747142269; hg19: chr14-75356070; COSMIC: COSV53166252; COSMIC: COSV53166252;