dbSNP rs902320: SUCLG2:p.Val425Ile (chr3-67360679-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. 13/17 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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.00600

Publications

16 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SUCLG2	NM_001177599.2 link	c.1273G>A	p.Val425Ile	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.1273G>A	p.Val425Ile	missense_variant	Exon 11 of 11	1		ENSP00000419325.1		Q96I99-2

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37282

AN:

151952

Hom.:

4692

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.241

AC:

31757

AN:

131920

AF XY:

0.239

show subpopulations

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 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.:

AF XY:

0.257

AC XY:

173547

AN XY:

674468

show subpopulations

African (AFR)

AF:

0.196

AC:

6149

AN:

31412

American (AMR)

AF:

0.236

AC:

8292

AN:

35202

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

3586

AN:

24760

East Asian (EAS)

AF:

0.261

AC:

9273

AN:

35522

South Asian (SAS)

AF:

0.226

AC:

17264

AN:

76436

European-Finnish (FIN)

AF:

0.344

AC:

11417

AN:

33212

Middle Eastern (MID)

AF:

0.112

AC:

631

AN:

5644

European-Non Finnish (NFE)

AF:

0.266

AC:

284114

AN:

1068470

Other (OTH)

AF:

0.241

AC:

13763

AN:

57162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

13091

26182

39274

52365

65456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9716

19432

29148

38864

48580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.245

AC:

37319

AN:

152070

Hom.:

4700

Cov.:

AF XY:

0.246

AC XY:

18285

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.203

AC:

8424

AN:

41490

American (AMR)

AF:

0.200

AC:

3052

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

502

AN:

3472

East Asian (EAS)

AF:

0.260

AC:

1347

AN:

5172

South Asian (SAS)

AF:

0.234

AC:

1128

AN:

4820

European-Finnish (FIN)

AF:

0.343

AC:

3617

AN:

10556

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.270

AC:

18370

AN:

67982

Other (OTH)

AF:

0.211

AC:

446

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1462

2924

4387

5849

7311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.255

Hom.:

10761

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.1

(source)

DANN

Benign

0.21

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.1

PhyloP100

-0.0060

PROVEAN

Benign

-0.28

REVEL

Benign

0.035

Sift

Uncertain

0.025

Sift4G

Benign

0.18

Vest4

0.028

MPC

0.053

ClinPred

0.012

GERP RS

1.6

gMVP

0.59

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over