13-47942710-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003850.3(SUCLA2):c.*661C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 152,236 control chromosomes in the GnomAD database, including 730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (730 hom., cov: 33)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: SUCLA2 NM_003850.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 13-47942710-G-T is Benign according to our data. Variant chr13-47942710-G-T is described in ClinVar as [Benign]. Clinvar id is 312254.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUCLA2	NM_003850.3	c.*661C>A		3_prime_UTR_variant	11/11	ENST00000646932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUCLA2	ENST00000646932.1	c.*661C>A		3_prime_UTR_variant	11/11		NM_003850.3	P1

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12865 AN: 152090 Hom.: 729 Cov.: 33

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.0770

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0234

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0724

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0714 AC: 2 AN: 28 Hom.: 0 Cov.: 0 AF XY: 0.0556 AC XY: 1 AN XY: 18

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0909

GnomAD4 genome AF: 0.0846 AC: 12874 AN: 152208 Hom.: 730 Cov.: 33 AF XY: 0.0846 AC XY: 6293 AN XY: 74422

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.0768

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.0237

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.0724

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.110

Alfa AF: 0.101 Hom.: 710

Bravo AF: 0.0816

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	8.0
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10397; hg19: chr13-48516845;