rs6561429

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.94).
• 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

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.0777

Gnomad4 NFE AF: 0.0886

Gnomad4 OTH AF: 0.169

Alfa AF: 0.163 Hom.: 275

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6561429; hg19: chr13-48577185;