rs9634811

Variant names:

• chr13-47890040-A-G
• rs9634811
• ENST00000643584.1:n.*214+15289T>C

Variant summary

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

The ENST00000643584.1(SUCLA2):​n.*214+15289T>C variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 2 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=-0.9).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLA2	ENST00000643584.1	n.*214+15289T>C		intron_variant	Intron 13 of 13			ENSP00000494987.1
SUCLA2	ENST00000647008.1	n.1237+16978T>C		intron_variant	Intron 4 of 7

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

African (AFR) AF: 0.102 AC: 4237 AN: 41534

American (AMR) AF: 0.0985 AC: 1506 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3470

East Asian (EAS) AF: 0.0231 AC: 120 AN: 5190

South Asian (SAS) AF: 0.220 AC: 1060 AN: 4816

European-Finnish (FIN) AF: 0.0843 AC: 893 AN: 10596

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8491 AN: 68012

Other (OTH) AF: 0.134 AC: 283 AN: 2106

Alfa AF: 0.127 Hom.: 1748

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
PhyloP100		0.036

Splicing

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

Other links and lift over

dbSNP: rs9634811; hg19: chr13-48464175;