rs8001976

chr13-47813587-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000643584.1(SUCLA2):c.*215-66163G>A variant causes a intron, NMD transcript 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, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUCLA2	ENST00000643584.1	c.*215-66163G>A		intron_variant, NMD_transcript_variant
SUCLA2	ENST00000647008.1	n.1238-6088G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.407

Alfa AF: 0.428 Hom.: 9883

Bravo AF: 0.419

Asia WGS AF: 0.416 AC: 1446 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.8
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8001976; hg19: chr13-48387722;