rs8001976

Variant names:

• chr13-47813587-C-T
• rs8001976
• ENST00000643584.1:n.*215-66163G>A

Variant summary

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

The ENST00000643584.1(SUCLA2):​n.*215-66163G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,878 control chromosomes in the GnomAD database, including 13,458 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.

• Frequency: Genomes: 𝑓 0.42 (13458 hom., cov: 32)
• Consequence: SUCLA2 ENST00000643584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 9 publications found

Genes affected

SUCLA2 (HGNC:11448): (succinate-CoA ligase ADP-forming subunit beta) Succinyl-CoA synthetase (SCS) is a mitochondrial matrix enzyme that acts as a heterodimer, being composed of an invariant alpha subunit and a substrate-specific beta subunit. The protein encoded by this gene is an ATP-specific SCS beta subunit that dimerizes with the SCS alpha subunit to form SCS-A, an essential component of the tricarboxylic acid cycle. SCS-A hydrolyzes ATP to convert succinate to succinyl-CoA. Defects in this gene are a cause of myopathic mitochondrial DNA depletion syndrome. A pseudogene of this gene has been found on chromosome 6. [provided by RefSeq, Jul 2008]

SUCLA2 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria

  Inheritance: Mitochondrial, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000643584.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLA2	ENST00000643584.1		n.*215-66163G>A		intron	N/A	ENSP00000494987.1
	SUCLA2	ENST00000647008.1		n.1238-6088G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63405 AN: 151758 Hom.: 13444 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.408

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.418 AC: 63464 AN: 151878 Hom.: 13458 Cov.: 32 AF XY: 0.418 AC XY: 31021 AN XY: 74242

African (AFR) AF: 0.386 AC: 15992 AN: 41390

American (AMR) AF: 0.413 AC: 6305 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1093 AN: 3468

East Asian (EAS) AF: 0.534 AC: 2752 AN: 5152

South Asian (SAS) AF: 0.370 AC: 1782 AN: 4822

European-Finnish (FIN) AF: 0.454 AC: 4791 AN: 10556

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29377 AN: 67922

Other (OTH) AF: 0.407 AC: 859 AN: 2110

Alfa AF: 0.429 Hom.: 28363

Bravo AF: 0.419

Asia WGS AF: 0.416 AC: 1446 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.8
DANN	Benign	0.59
PhyloP100		0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8001976; hg19: chr13-48387722;