rs7986369

Positions:

• chr13-47888988-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000643584.1(SUCLA2):​c.*214+16341G>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 152,018 control chromosomes in the GnomAD database, including 12,516 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 0.40 (12516 hom., cov: 32)
• Consequence: SUCLA2 ENST00000643584.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 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	ENST00000643584.1	c.*214+16341G>T		intron_variant, NMD_transcript_variant				ENSP00000494987
SUCLA2	ENST00000647008.1	n.1237+18030G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60199 AN: 151900 Hom.: 12512 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.396 AC: 60228 AN: 152018 Hom.: 12516 Cov.: 32 AF XY: 0.386 AC XY: 28682 AN XY: 74294

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.383

Alfa AF: 0.379 Hom.: 6320

Bravo AF: 0.399

Asia WGS AF: 0.254 AC: 884 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	2.3
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7986369; hg19: chr13-48463123;