13-47854380-C-T

Variant names:

• chr13-47854380-C-T
• rs1408617
• ENST00000643584.1:n.*214+50949G>A

Variant summary

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

The ENST00000643584.1(SUCLA2):​n.*214+50949G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 151,984 control chromosomes in the GnomAD database, including 22,595 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 0.54 (22595 hom., cov: 32)
• Consequence: SUCLA2 ENST00000643584.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740

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 (EAS) allele frequency at 95% confidence interval = 0.64 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	ENST00000643584.1	n.*214+50949G>A		intron_variant	Intron 13 of 13			ENSP00000494987.1
SUCLA2	ENST00000647008.1	n.1238-46881G>A		intron_variant	Intron 4 of 7

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81944 AN: 151866 Hom.: 22586 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.539 AC: 81986 AN: 151984 Hom.: 22595 Cov.: 32 AF XY: 0.540 AC XY: 40113 AN XY: 74276

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.659

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.521

Alfa AF: 0.588 Hom.: 43352

Bravo AF: 0.528

Asia WGS AF: 0.591 AC: 2055 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	1.5
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1408617; hg19: chr13-48428515;