Genetic Variant ENST00000493112.5:c.1210T>C (chr3-67360742-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.25

Variant links:

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]

SUCLG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
SUCLG2	NM_001177599.2 link	c.1210T>C	p.Tyr404His	missense_variant	Exon 11 of 11		NP_001171070.1	Q96I99-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLG2	ENST00000493112.5 link	c.1210T>C	p.Tyr404His	missense_variant	Exon 11 of 11	1		ENSP00000419325.1		Q96I99-2

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

60979

AN:

151840

Hom.:

12302

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.386

AC XY:

260578

AN XY:

675806

show subpopulations

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.:

AF XY:

0.400

AC XY:

29716

AN XY:

74248

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.59

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

LIST_S2

Benign

0.35

MetaRNN

Benign

0.00078

MetaSVM

Benign

-0.96

PROVEAN

Benign

0.20

REVEL

Benign

0.081

Sift

Benign

0.18

Sift4G

Benign

0.60

Vest4

0.072

MPC

0.065

ClinPred

0.0013

GERP RS

3.2

gMVP

0.49

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over