chr13-48003049-A-G

Position:

• chr13-48003049-A-G

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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUCLA2	ENST00000643246.1	c.-84-6026T>C		intron_variant				ENSP00000496235
SUCLA2	ENST00000646804.1	c.-84-6026T>C		intron_variant				ENSP00000493977

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;