chr13-47988873-G-A

Variant names:

• chr13-47988873-G-A
• rs6561424
• NM_003850.3:c.371+9C>T

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.371+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,610,790 control chromosomes in the GnomAD database, including 503,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (41387 hom., cov: 33)
  • Exomes 𝑓: 0.79 (462492 hom.)
• Consequence: SUCLA2 NM_003850.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.800
• Publications: 17 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 13-47988873-G-A is Benign according to our data. Variant chr13-47988873-G-A is described in ClinVar as Benign. ClinVar VariationId is 139358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.809 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.371+9C>T		intron	N/A	NP_003841.1	E5KS60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLA2	ENST00000646932.1	MANE Select	c.371+9C>T		intron	N/A	ENSP00000494360.1	Q9P2R7-1
	SUCLA2	ENST00000643023.1		c.371+9C>T		intron	N/A	ENSP00000495664.1	A0A2R8Y6Y7
	SUCLA2	ENST00000853364.1		c.428+9C>T		intron	N/A	ENSP00000523423.1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110878 AN: 151976 Hom.: 41382 Cov.: 33

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.761

GnomAD2 exomes AF: 0.748 AC: 187378 AN: 250556 AF XY: 0.750

Gnomad AFR exome AF: 0.581

Gnomad AMR exome AF: 0.635

Gnomad ASJ exome AF: 0.780

Gnomad EAS exome AF: 0.792

Gnomad FIN exome AF: 0.792

Gnomad NFE exome AF: 0.818

Gnomad OTH exome AF: 0.761

GnomAD4 exome AF: 0.793 AC: 1157108 AN: 1458696 Hom.: 462492 Cov.: 37 AF XY: 0.789 AC XY: 572835 AN XY: 725764

African (AFR) AF: 0.571 AC: 19052 AN: 33394

American (AMR) AF: 0.638 AC: 28502 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 20442 AN: 26122

East Asian (EAS) AF: 0.780 AC: 30908 AN: 39638

South Asian (SAS) AF: 0.636 AC: 54781 AN: 86114

European-Finnish (FIN) AF: 0.791 AC: 41930 AN: 52998

Middle Eastern (MID) AF: 0.726 AC: 3286 AN: 4528

European-Non Finnish (NFE) AF: 0.820 AC: 911038 AN: 1111004

Other (OTH) AF: 0.784 AC: 47169 AN: 60190

GnomAD4 genome AF: 0.729 AC: 110913 AN: 152094 Hom.: 41387 Cov.: 33 AF XY: 0.728 AC XY: 54104 AN XY: 74366

African (AFR) AF: 0.583 AC: 24166 AN: 41440

American (AMR) AF: 0.675 AC: 10316 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2765 AN: 3472

East Asian (EAS) AF: 0.797 AC: 4131 AN: 5180

South Asian (SAS) AF: 0.623 AC: 3002 AN: 4818

European-Finnish (FIN) AF: 0.797 AC: 8444 AN: 10590

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55424 AN: 68000

Other (OTH) AF: 0.761 AC: 1608 AN: 2112

Alfa AF: 0.778 Hom.: 27377

Bravo AF: 0.715

Asia WGS AF: 0.689 AC: 2392 AN: 3476

EpiCase AF: 0.809

EpiControl AF: 0.806

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (3)
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.64
PhyloP100		0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6561424; hg19: chr13-48563008;