rs1799900

Variant names:

• chr14-74901037-G-A
• rs1799900
• NM_001933.5:c.1060-29G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-74901037-G-A
• chr14-74901037-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pheochromocytoma/paraganglioma syndrome 7

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• pyruvate dehydrogenase E1-alpha deficiency

  Inheritance: AR Classification: NO_KNOWN Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001933.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLST	NM_001933.5	MANE Select	c.1060-29G>A		intron	N/A	NP_001924.2
	DLST	NR_033814.2		n.1040-29G>A		intron	N/A
	DLST	NR_045209.2		n.1049-29G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLST	ENST00000334220.9	TSL:1 MANE Select	c.1060-29G>A		intron	N/A	ENSP00000335304.4	P36957-1
	DLST	ENST00000555089.5	TSL:1	n.*689-29G>A		intron	N/A	ENSP00000452422.1	G3V5M3
	DLST	ENST00000875051.1		c.1057-29G>A		intron	N/A	ENSP00000545110.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98584 AN: 152052 Hom.: 33999 Cov.: 33

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

GnomAD2 exomes AF: 0.573 AC: 142463 AN: 248454 AF XY: 0.573

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 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.: 32 AF XY: 0.556 AC XY: 402937 AN XY: 724232

African (AFR) AF: 0.928 AC: 30889 AN: 33270

American (AMR) AF: 0.494 AC: 21857 AN: 44242

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 14006 AN: 25896

East Asian (EAS) AF: 0.489 AC: 19377 AN: 39632

South Asian (SAS) AF: 0.659 AC: 56508 AN: 85736

European-Finnish (FIN) AF: 0.644 AC: 34278 AN: 53246

Middle Eastern (MID) AF: 0.560 AC: 3155 AN: 5638

European-Non Finnish (NFE) AF: 0.535 AC: 592984 AN: 1108026

Other (OTH) AF: 0.555 AC: 33374 AN: 60120

GnomAD4 genome AF: 0.649 AC: 98695 AN: 152172 Hom.: 34054 Cov.: 33 AF XY: 0.652 AC XY: 48465 AN XY: 74372

African (AFR) AF: 0.907 AC: 37709 AN: 41568

American (AMR) AF: 0.539 AC: 8241 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1906 AN: 3466

East Asian (EAS) AF: 0.449 AC: 2319 AN: 5170

South Asian (SAS) AF: 0.673 AC: 3242 AN: 4820

European-Finnish (FIN) AF: 0.668 AC: 7056 AN: 10560

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36224 AN: 67984

Other (OTH) AF: 0.618 AC: 1307 AN: 2116

Alfa AF: 0.565 Hom.: 17234

Bravo AF: 0.646

Asia WGS AF: 0.616 AC: 2141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.72
PhyloP100		0.26
BranchPoint Hunter		2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1799900; hg19: chr14-75367740; COSMIC: COSV53168073; COSMIC: COSV53168073;