3-67360679-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000493112.5(SUCLG2):c.1273G>A(p.Val425Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,519,890 control chromosomes in the GnomAD database, including 51,862 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4700 hom., cov: 33)
  • Exomes 𝑓: 0.26 (47162 hom.)
• Consequence: SUCLG2 ENST00000493112.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00600

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002345711).
• BP6: Variant 3-67360679-C-T is Benign according to our data. Variant chr3-67360679-C-T is described in ClinVar as [Benign]. Clinvar id is 257600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUCLG2	NM_001177599.2	c.1273G>A	p.Val425Ile	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUCLG2	ENST00000493112.5	c.1273G>A	p.Val425Ile	missense_variant	11/11	1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37282 AN: 151952 Hom.: 4692 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.205

GnomAD3 exomes AF: 0.241 AC: 31757 AN: 131920 Hom.: 4157 AF XY: 0.239 AC XY: 17194 AN XY: 71876

Gnomad AFR exome AF: 0.188

Gnomad AMR exome AF: 0.232

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.260

Gnomad SAS exome AF: 0.224

Gnomad FIN exome AF: 0.353

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.259 AC: 354489 AN: 1367820 Hom.: 47162 Cov.: 31 AF XY: 0.257 AC XY: 173547 AN XY: 674468

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.226

Gnomad4 FIN exome AF: 0.344

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.245 AC: 37319 AN: 152070 Hom.: 4700 Cov.: 33 AF XY: 0.246 AC XY: 18285 AN XY: 74324

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.211

Alfa AF: 0.255 Hom.: 8054

Bravo AF: 0.233

TwinsUK AF: 0.270 AC: 1003

ALSPAC AF: 0.268 AC: 1031

ExAC AF: 0.195 AC: 2866

Asia WGS AF: 0.275 AC: 958 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	8.1
Dann	Benign	0.21
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.035
Sift	Uncertain	0.025	D
Sift4G	Benign	0.18	T
Vest4		0.028
MPC		0.053
ClinPred		0.012	T
GERP RS		1.6
gMVP		0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs902320; hg19: chr3-67411103;