rs7986369

Variant names:

• chr13-47888988-C-A
• rs7986369
• ENST00000643584.1:n.*214+16341G>T

Variant summary

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

The ENST00000643584.1(SUCLA2):​n.*214+16341G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,018 control chromosomes in the GnomAD database, including 12,516 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 0.40 (12516 hom., cov: 32)
• Consequence: SUCLA2 ENST00000643584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLA2	ENST00000643584.1	n.*214+16341G>T		intron_variant	Intron 13 of 13			ENSP00000494987.1
SUCLA2	ENST00000647008.1	n.1237+18030G>T		intron_variant	Intron 4 of 7

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60199 AN: 151900 Hom.: 12512 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.396 AC: 60228 AN: 152018 Hom.: 12516 Cov.: 32 AF XY: 0.386 AC XY: 28682 AN XY: 74294

African (AFR) AF: 0.508 AC: 21054 AN: 41454

American (AMR) AF: 0.287 AC: 4377 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1269 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1175 AN: 5172

South Asian (SAS) AF: 0.277 AC: 1336 AN: 4822

European-Finnish (FIN) AF: 0.317 AC: 3350 AN: 10560

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26291 AN: 67956

Other (OTH) AF: 0.383 AC: 807 AN: 2108

Alfa AF: 0.382 Hom.: 8560

Bravo AF: 0.399

Asia WGS AF: 0.254 AC: 884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.59
PhyloP100		-0.0080

Splicing

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

Other links and lift over

dbSNP: rs7986369; hg19: chr13-48463123;