rs9634811

chr13-47890040-A-G

Variant summary

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

The ENST00000643584.1(SUCLA2):c.*214+15289T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,220 control chromosomes in the GnomAD database, including 1,073 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 0.11 (1073 hom., cov: 32)
• Consequence: SUCLA2 ENST00000643584.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 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.*214+15289T>C		intron_variant, NMD_transcript_variant
SUCLA2	ENST00000647008.1	n.1237+16978T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17291 AN: 152102 Hom.: 1070 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0987

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.0229

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.0843

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.114 AC: 17305 AN: 152220 Hom.: 1073 Cov.: 32 AF XY: 0.114 AC XY: 8458 AN XY: 74412

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0985

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.0231

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.0843

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.134

Alfa AF: 0.128 Hom.: 1443

Bravo AF: 0.112

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.1
Dann	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9634811; hg19: chr13-48464175;