rs11620399

Variant names:

• chr13-47862790-G-T
• rs11620399
• ENST00000643584.1:n.*214+42539C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000643584.1(SUCLA2):​n.*214+42539C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 in 152,070 control chromosomes in the GnomAD database, including 139 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 0.035 (139 hom., cov: 32)
• Consequence: SUCLA2 ENST00000643584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244
• Publications: 5 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).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0349 (5307/152070) while in subpopulation NFE AF = 0.0513 (3486/67994). AF 95% confidence interval is 0.0498. There are 139 homozygotes in GnomAd4. There are 2641 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 139 Mitochondrial,AR gene

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+42539C>A		intron_variant	Intron 13 of 13			ENSP00000494987.1
SUCLA2	ENST00000647008.1	n.1237+44228C>A		intron_variant	Intron 4 of 7

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5308 AN: 151952 Hom.: 139 Cov.: 32

Gnomad AFR AF: 0.00834

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0278

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00961

Gnomad FIN AF: 0.0804

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0513

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0349 AC: 5307 AN: 152070 Hom.: 139 Cov.: 32 AF XY: 0.0355 AC XY: 2641 AN XY: 74324

African (AFR) AF: 0.00832 AC: 345 AN: 41474

American (AMR) AF: 0.0277 AC: 424 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.00962 AC: 46 AN: 4784

European-Finnish (FIN) AF: 0.0804 AC: 849 AN: 10566

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0513 AC: 3486 AN: 67994

Other (OTH) AF: 0.0327 AC: 69 AN: 2112

Alfa AF: 0.0327 Hom.: 28

Bravo AF: 0.0302

Asia WGS AF: 0.00375 AC: 13 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	2.2
DANN	Benign	0.63
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs11620399; hg19: chr13-48436925;