2-84423759-C-T

Variant names:

• chr2-84423759-C-T
• NM_003849.4:c.1028G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003849.4(SUCLG1):​c.1028G>A​(p.Arg343Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,453,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SUCLG1 NM_003849.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.66

Genes affected

SUCLG1 (HGNC:11449): (succinate-CoA ligase GDP/ADP-forming subunit alpha) This gene encodes the alpha subunit of the heterodimeric enzyme succinate coenzyme A ligase. This enzyme is targeted to the mitochondria and catalyzes the conversion of succinyl CoA and ADP or GDP to succinate and ATP or GTP. Mutations in this gene are the cause of the metabolic disorder fatal infantile lactic acidosis and mitochondrial DNA depletion. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2783133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCLG1	NM_003849.4	c.1028G>A	p.Arg343Lys	missense_variant	Exon 9 of 9	ENST00000393868.7	NP_003840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLG1	ENST00000393868.7	c.1028G>A	p.Arg343Lys	missense_variant	Exon 9 of 9	1	NM_003849.4	ENSP00000377446.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1453922 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 722716

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000361

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.065
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	0.0050	N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.68	N
REVEL	Uncertain	0.35
Sift	Benign	0.26	T
Sift4G	Benign	0.51	T
Polyphen		0.0	B
Vest4		0.52
MutPred		0.47		Gain of methylation at R343 (P = 0.0115);
MVP		0.85
MPC		0.040
ClinPred		0.89	D
GERP RS		4.7
Varity_R		0.50
gMVP		0.57

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-84650883;