13-48003049-A-G

Variant names:

• chr13-48003049-A-G
• rs6561429
• ENST00000646804.1:c.-84-6026T>C

Variant summary

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

The ENST00000646804.1(SUCLA2):​c.-84-6026T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,084 control chromosomes in the GnomAD database, including 4,076 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 0.19 (4076 hom., cov: 32)
• Consequence: SUCLA2 ENST00000646804.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 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	ENST00000646804.1	c.-84-6026T>C		intron_variant	Intron 1 of 10			ENSP00000493977.1
SUCLA2	ENST00000643246.1	c.-84-6026T>C		intron_variant	Intron 2 of 2			ENSP00000496235.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28837 AN: 151966 Hom.: 4051 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.0777

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0886

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.190 AC: 28915 AN: 152084 Hom.: 4076 Cov.: 32 AF XY: 0.188 AC XY: 14006 AN XY: 74368

African (AFR) AF: 0.382 AC: 15827 AN: 41412

American (AMR) AF: 0.233 AC: 3567 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3472

East Asian (EAS) AF: 0.179 AC: 924 AN: 5168

South Asian (SAS) AF: 0.176 AC: 849 AN: 4828

European-Finnish (FIN) AF: 0.0777 AC: 822 AN: 10582

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0886 AC: 6026 AN: 68010

Other (OTH) AF: 0.169 AC: 357 AN: 2114

Alfa AF: 0.123 Hom.: 2757

Bravo AF: 0.212

Asia WGS AF: 0.202 AC: 702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.3
DANN	Benign	0.28
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6561429; hg19: chr13-48577185;