ENST00000493112.5:c.1291A>T

Variant names:

• chr3-67360661-T-A
• rs998614942
• ENST00000493112.5:c.1291A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000493112.5(SUCLG2):​c.1291A>T​(p.Ser431Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000293 in 1,365,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict 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. S431G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: SUCLG2 ENST00000493112.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200
• Publications: 0 publications found

Genes affected

SUCLG2 (HGNC:11450): (succinate-CoA ligase GDP-forming subunit beta) This gene encodes a GTP-specific beta subunit of succinyl-CoA synthetase. Succinyl-CoA synthetase catalyzes the reversible reaction involving the formation of succinyl-CoA and succinate. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 5 and 12. [provided by RefSeq, Apr 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14519054).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000493112.5. 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
	SUCLG2	NM_001177599.2		c.1291A>T	p.Ser431Cys	missense	Exon 11 of 11	NP_001171070.1	Q96I99-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLG2	ENST00000493112.5	TSL:1	c.1291A>T	p.Ser431Cys	missense	Exon 11 of 11	ENSP00000419325.1	Q96I99-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000293 AC: 4 AN: 1365332 Hom.: 0 Cov.: 29 AF XY: 0.00000446 AC XY: 3 AN XY: 673122

African (AFR) AF: 0.00 AC: 0 AN: 31342

American (AMR) AF: 0.00 AC: 0 AN: 34874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24616

East Asian (EAS) AF: 0.00 AC: 0 AN: 35586

South Asian (SAS) AF: 0.00 AC: 0 AN: 75628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5626

European-Non Finnish (NFE) AF: 0.00000375 AC: 4 AN: 1067580

Other (OTH) AF: 0.00 AC: 0 AN: 56998

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.97
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.74	T
PhyloP100		0.20
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.074
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.010	D
Vest4		0.19
MutPred		0.44		Gain of helix (P = 0.0143)
MVP		0.66
MPC		0.091
ClinPred		0.11	T
GERP RS		-0.34
gMVP		0.61
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs998614942; hg19: chr3-67411085;