3-67360707-A-C

Variant names:

• chr3-67360707-A-C
• rs192811331
• ENST00000493112.5:c.1245T>G

Variant summary

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

The NM_001177599.2(SUCLG2):​c.1245T>G​(p.Asn415Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,379,436 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: SUCLG2 NM_001177599.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.503
• 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=0.1374825).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177599.2. 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.1245T>G	p.Asn415Lys	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.1245T>G	p.Asn415Lys	missense	Exon 11 of 11	ENSP00000419325.1	Q96I99-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1379436 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 680534

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31522

American (AMR) AF: 0.00 AC: 0 AN: 35562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25076

East Asian (EAS) AF: 0.00 AC: 0 AN: 35686

South Asian (SAS) AF: 0.00 AC: 0 AN: 78372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33682

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00000279 AC: 3 AN: 1076138

Other (OTH) AF: 0.00 AC: 0 AN: 57714

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.67
DANN	Benign	0.48
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.92	T
PhyloP100		0.50
PROVEAN	Benign	0.48	N
REVEL	Benign	0.057
Sift	Benign	0.19	T
Sift4G	Benign	0.17	T
Vest4		0.16
MutPred		0.56		Gain of ubiquitination at N415 (P = 0.0109)
MVP		0.65
MPC		0.059
ClinPred		0.040	T
GERP RS		0.74
gMVP		0.57
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: rs192811331; hg19: chr3-67411131;