rs11620399

chr13-47862790-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000643584.1(SUCLA2):c.*214+42539C>A variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0349 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, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

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).
• 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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 139 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUCLA2	ENST00000643584.1	c.*214+42539C>A		intron_variant, NMD_transcript_variant
SUCLA2	ENST00000647008.1	n.1237+44228C>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.00832

Gnomad4 AMR AF: 0.0277

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00962

Gnomad4 FIN AF: 0.0804

Gnomad4 NFE AF: 0.0513

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.0347 Hom.: 27

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11620399; hg19: chr13-48436925;