rs902321

chr3-67360742-A-Gchr3-67360742-A-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.1210T>C(p.Tyr404His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,522,522 control chromosomes in the GnomAD database, including 117,134 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 0.40 (12309 hom., cov: 32)
  • Exomes 𝑓: 0.39 (104825 hom.)
• Consequence: SUCLG2 ENST00000493112.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.25

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=7.7676773E-4).
• BP6: Variant 3-67360742-A-G is Benign according to our data. Variant chr3-67360742-A-G is described in ClinVar as [Benign]. Clinvar id is 257599.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUCLG2	NM_001177599.2	c.1210T>C	p.Tyr404His	missense_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUCLG2	ENST00000493112.5	c.1210T>C	p.Tyr404His	missense_variant	11/11	1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60979 AN: 151840 Hom.: 12302 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.367

GnomAD3 exomes AF: 0.378 AC: 48097 AN: 127338 Hom.: 9312 AF XY: 0.374 AC XY: 25906 AN XY: 69178

Gnomad AFR exome AF: 0.433

Gnomad AMR exome AF: 0.327

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.467

Gnomad SAS exome AF: 0.312

Gnomad FIN exome AF: 0.478

Gnomad NFE exome AF: 0.397

Gnomad OTH exome AF: 0.363

GnomAD4 exome AF: 0.389 AC: 532905 AN: 1370566 Hom.: 104825 Cov.: 31 AF XY: 0.386 AC XY: 260578 AN XY: 675806

Gnomad4 AFR exome AF: 0.437

Gnomad4 AMR exome AF: 0.334

Gnomad4 ASJ exome AF: 0.347

Gnomad4 EAS exome AF: 0.449

Gnomad4 SAS exome AF: 0.310

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.392

Gnomad4 OTH exome AF: 0.385

GnomAD4 genome AF: 0.402 AC: 61028 AN: 151956 Hom.: 12309 Cov.: 32 AF XY: 0.400 AC XY: 29716 AN XY: 74248

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.372

Alfa AF: 0.393 Hom.: 15361

Bravo AF: 0.396

TwinsUK AF: 0.383 AC: 1419

ALSPAC AF: 0.381 AC: 1469

ExAC AF: 0.312 AC: 4449

Asia WGS AF: 0.419 AC: 1456 AN: 3476

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

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- -

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	-0.59	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	2.6
Dann	Benign	0.66
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.00078	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P
PROVEAN	Benign	0.20	N
REVEL	Benign	0.081
Sift	Benign	0.18	T
Sift4G	Benign	0.60	T
Vest4		0.072
MPC		0.065
ClinPred		0.0013	T
GERP RS		3.2
gMVP		0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs902321; hg19: chr3-67411166; COSMIC: COSV72330715;