3-67360742-A-T

Variant names:

• chr3-67360742-A-T
• rs902321
• ENST00000493112.5:c.1210T>A

Variant summary

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

The ENST00000493112.5(SUCLG2):​c.1210T>A​(p.Tyr404Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,373,234 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. Y404H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: SUCLG2 ENST00000493112.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 14 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2798027).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLG2	NM_001177599.2		c.1210T>A	p.Tyr404Asn	missense	Exon 11 of 11	NP_001171070.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLG2	ENST00000493112.5	TSL:1	c.1210T>A	p.Tyr404Asn	missense	Exon 11 of 11	ENSP00000419325.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1373234 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 677050

African (AFR) AF: 0.00 AC: 0 AN: 31166

American (AMR) AF: 0.00 AC: 0 AN: 33564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24850

East Asian (EAS) AF: 0.00 AC: 0 AN: 35654

South Asian (SAS) AF: 0.00 AC: 0 AN: 76668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 9.31e-7 AC: 1 AN: 1074532

Other (OTH) AF: 0.00 AC: 0 AN: 57476

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 37823

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	4.2
DANN	Benign	0.61
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.65	T
PhyloP100		1.3
PROVEAN	Benign	0.54	N
REVEL	Benign	0.081
Sift	Benign	0.11	T
Sift4G	Benign	0.41	T
Vest4		0.33
MutPred		0.56		Gain of loop (P = 0.0045)
MVP		0.81
MPC		0.080
ClinPred		0.062	T
GERP RS		3.2
gMVP		0.52
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: rs902321; hg19: chr3-67411166;