13-48001432-C-CG

Variant names:

• chr13-48001432-C-CG
• rs149342330
• ENST00000423869.2:n.47dupG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000646804.1(SUCLA2):​c.-84-4410dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUCLA2 ENST00000646804.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55
• Publications: 0 publications found

Genes affected

SUCLA2-AS1 (HGNC:39965): (SUCLA2 antisense RNA 1)

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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000646804.1. 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-AS1	NR_189308.1		n.31dupG		non_coding_transcript_exon	Exon 1 of 2
	SUCLA2	NM_003850.3	MANE Select	c.-164dupC		upstream_gene	N/A	NP_003841.1	E5KS60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLA2-AS1	ENST00000423869.2	TSL:1	n.47dupG		non_coding_transcript_exon	Exon 1 of 2
	SUCLA2	ENST00000646804.1		c.-84-4410dupC		intron	N/A	ENSP00000493977.1	A0A2R8YDQ9
	SUCLA2	ENST00000643246.1		c.-84-4410dupC		intron	N/A	ENSP00000496235.1	A0A2R8YF84

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 6

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.6

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs149342330;

hg19: chr13-48575568;