13-47854380-C-T

Variant names:

• chr13-47854380-C-T
• rs1408617
• ENST00000643584.1:n.*214+50949G>A

Variant summary

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

The ENST00000643584.1(SUCLA2):​n.*214+50949G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,984 control chromosomes in the GnomAD database, including 22,595 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 0.54 (22595 hom., cov: 32)
• Consequence: SUCLA2 ENST00000643584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740
• Publications: 3 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: AR, Mitochondrial Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.64 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

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLA2	ENST00000643584.1		n.*214+50949G>A		intron	N/A	ENSP00000494987.1	Q9P2R7-1
	SUCLA2	ENST00000647008.1		n.1238-46881G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81944 AN: 151866 Hom.: 22586 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.539 AC: 81986 AN: 151984 Hom.: 22595 Cov.: 32 AF XY: 0.540 AC XY: 40113 AN XY: 74276

African (AFR) AF: 0.422 AC: 17498 AN: 41426

American (AMR) AF: 0.498 AC: 7597 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2042 AN: 3470

East Asian (EAS) AF: 0.659 AC: 3406 AN: 5172

South Asian (SAS) AF: 0.586 AC: 2822 AN: 4812

European-Finnish (FIN) AF: 0.560 AC: 5910 AN: 10552

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40880 AN: 67972

Other (OTH) AF: 0.521 AC: 1100 AN: 2110

Alfa AF: 0.579 Hom.: 97140

Bravo AF: 0.528

Asia WGS AF: 0.591 AC: 2055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.74
PhyloP100		-0.74

Splicing

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

Other links and lift over

dbSNP: rs1408617; hg19: chr13-48428515;