13-48001202-G-T

Variant names:

• chr13-48001202-G-T
• rs538760468
• NM_003850.3:c.68C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003850.3(SUCLA2):​c.68C>A​(p.Thr23Lys) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T23M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SUCLA2 NM_003850.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.13
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36429405).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLA2	NM_003850.3	MANE Select	c.68C>A	p.Thr23Lys	missense	Exon 1 of 11	NP_003841.1
	SUCLA2-AS1	NR_189308.1		n.-203G>T		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLA2	ENST00000646932.1	MANE Select	c.68C>A	p.Thr23Lys	missense	Exon 1 of 11	ENSP00000494360.1
	SUCLA2	ENST00000643023.1		c.68C>A	p.Thr23Lys	missense	Exon 1 of 12	ENSP00000495664.1
	SUCLA2	ENST00000434484.5	TSL:5	c.39C>A	p.Asp13Glu	missense	Exon 1 of 7	ENSP00000392771.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.21	T
M_CAP	Pathogenic	0.88	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.87	T
PhyloP100		6.1
PROVEAN	Benign	0.59	N
REVEL	Uncertain	0.34
Sift	Benign	0.36	T
Sift4G	Benign	1.0	T
MutPred		0.43		Gain of glycosylation at P10 (P = 0.1109)
MVP		0.75
ClinPred		0.62	D
GERP RS		4.9
PromoterAI		0.12	Neutral
Varity_R		0.17
Mutation Taster		=93/7	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

Other links and lift over

dbSNP: rs538760468; hg19: chr13-48575338;