13-47942710-G-T

Variant names:

• chr13-47942710-G-T
• rs10397
• NM_003850.3:c.*661C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.02
• Publications: 8 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: Mitochondrial, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 312254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

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.*661C>A		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.*661C>A		3_prime_UTR	Exon 11 of 11	ENSP00000494360.1	Q9P2R7-1
	SUCLA2	ENST00000643023.1		c.*661C>A		3_prime_UTR	Exon 12 of 12	ENSP00000495664.1	A0A2R8Y6Y7
	SUCLA2	ENST00000853364.1		c.*661C>A		3_prime_UTR	Exon 12 of 12	ENSP00000523423.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0909 AC: 2 AN: 22

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0260 AC: 1080 AN: 41538

American (AMR) AF: 0.0768 AC: 1175 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3468

East Asian (EAS) AF: 0.0237 AC: 123 AN: 5194

South Asian (SAS) AF: 0.180 AC: 868 AN: 4824

European-Finnish (FIN) AF: 0.0724 AC: 767 AN: 10596

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7816 AN: 67984

Other (OTH) AF: 0.110 AC: 231 AN: 2106

Alfa AF: 0.102 Hom.: 908

Bravo AF: 0.0816

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.0
DANN	Benign	0.49
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10397; hg19: chr13-48516845;