13-47943239-T-C

Variant names:

• chr13-47943239-T-C
• rs115959143
• NM_003850.3:c.*132A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_003850.3(SUCLA2):​c.*132A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000942 in 903,152 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (1 hom.)
• Consequence: SUCLA2 NM_003850.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21
• Publications: 0 publications found

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]

SUCLA2 Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria

  Inheritance: AR, Mitochondrial Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 13-47943239-T-C is Benign according to our data. Variant chr13-47943239-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1219029.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00358 (545/152302) while in subpopulation AFR AF = 0.0124 (517/41562). AF 95% confidence interval is 0.0116. There are 1 homozygotes in GnomAd4. There are 239 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003850.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLA2	NM_003850.3	MANE Select	c.*132A>G		3_prime_UTR	Exon 11 of 11	NP_003841.1	E5KS60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLA2	ENST00000646932.1	MANE Select	c.*132A>G		3_prime_UTR	Exon 11 of 11	ENSP00000494360.1	Q9P2R7-1
	SUCLA2	ENST00000643023.1		c.*132A>G		3_prime_UTR	Exon 12 of 12	ENSP00000495664.1	A0A2R8Y6Y7
	SUCLA2	ENST00000853364.1		c.*132A>G		3_prime_UTR	Exon 12 of 12	ENSP00000523423.1

Frequencies

GnomAD3 genomes AF: 0.00358 AC: 545 AN: 152184 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000408 AC: 306 AN: 750850 Hom.: 1 Cov.: 10 AF XY: 0.000370 AC XY: 148 AN XY: 400474

African (AFR) AF: 0.0115 AC: 228 AN: 19778

American (AMR) AF: 0.000682 AC: 29 AN: 42524

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21310

East Asian (EAS) AF: 0.00 AC: 0 AN: 35968

South Asian (SAS) AF: 0.0000282 AC: 2 AN: 70806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2726

European-Non Finnish (NFE) AF: 0.0000340 AC: 16 AN: 470280

Other (OTH) AF: 0.000848 AC: 31 AN: 36544

GnomAD4 genome AF: 0.00358 AC: 545 AN: 152302 Hom.: 1 Cov.: 32 AF XY: 0.00321 AC XY: 239 AN XY: 74474

African (AFR) AF: 0.0124 AC: 517 AN: 41562

American (AMR) AF: 0.00137 AC: 21 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00152 Hom.: 1

Bravo AF: 0.00386

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.6
DANN	Benign	0.52
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs115959143; hg19: chr13-48517374;