13-47942656-T-TC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_003850.3(SUCLA2):c.*714_*715insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 152,312 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.011 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SUCLA2 NM_003850.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0130

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0112 (1701/152312) while in subpopulation NFE AF= 0.0175 (1191/68030). AF 95% confidence interval is 0.0167. There are 12 homozygotes in gnomad4. There are 810 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUCLA2	NM_003850.3	c.*714_*715insG		3_prime_UTR_variant	11/11	ENST00000646932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUCLA2	ENST00000646932.1	c.*714_*715insG		3_prime_UTR_variant	11/11		NM_003850.3	P1

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1702 AN: 152194 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00335

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0175

Gnomad OTH AF: 0.0134

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 60 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 42

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0112 AC: 1701 AN: 152312 Hom.: 12 Cov.: 32 AF XY: 0.0109 AC XY: 810 AN XY: 74484

Gnomad4 AFR AF: 0.00334

Gnomad4 AMR AF: 0.0100

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.0175

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00443 Hom.: 0

Bravo AF: 0.0113

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mitochondrial DNA depletion syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs563064046; hg19: chr13-48516791;