13-48001192-C-G

Variant names:

• chr13-48001192-C-G
• NM_003850.3:c.78G>C
• SUCLA2 p.Arg26Arg

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003850.3(SUCLA2):​c.78G>C​(p.Arg26Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R26R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SUCLA2 NM_003850.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• 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-AS1 (HGNC:39965): (SUCLA2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14037064).
• BP7: Synonymous conserved (PhyloP=-0.151 with no splicing effect.

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.78G>C	p.Arg26Arg	synonymous	Exon 1 of 11	NP_003841.1	E5KS60
	SUCLA2-AS1	NR_189308.1		n.-213C>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLA2	ENST00000646932.1	MANE Select	c.78G>C	p.Arg26Arg	synonymous	Exon 1 of 11	ENSP00000494360.1	Q9P2R7-1
	SUCLA2	ENST00000434484.5	TSL:5	c.49G>C	p.Gly17Arg	missense	Exon 1 of 7	ENSP00000392771.1	Q5T9Q5
	SUCLA2	ENST00000643023.1		c.78G>C	p.Arg26Arg	synonymous	Exon 1 of 12	ENSP00000495664.1	A0A2R8Y6Y7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	6.2
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.70	T
PhyloP100		-0.15
PROVEAN	Benign	0.21	N
REVEL	Benign	0.16
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.11	T
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=299/1	polymorphism

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

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

Other links and lift over

hg19: chr13-48575328;