NM_003848.4:c.1141C>T

Variant names:

Variant summary

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

The NM_003848.4(SUCLG2):c.1141C>T(p.Arg381Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,611,788 control chromosomes in the GnomAD database, including 1,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R381Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.054 ( 691 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 640 hom. )

Consequence

SUCLG2
NM_003848.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.02

Publications

9 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=0.001975894).

BP6

Variant 3-67400773-G-A is Benign according to our data. Variant chr3-67400773-G-A is described in ClinVar as Benign. ClinVar VariationId is 257598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCLG2	NM_003848.4 link	c.1141C>T	p.Arg381Trp	missense_variant	Exon 10 of 11	ENST00000307227.10	NP_003839.2	Q96I99-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SUCLG2	ENST00000307227.10 link	c.1141C>T	p.Arg381Trp	missense_variant	Exon 10 of 11	1	NM_003848.4	ENSP00000307432.5	Q96I99-1
SUCLG2	ENST00000493112.5 link	c.1141C>T	p.Arg381Trp	missense_variant	Exon 10 of 11	1		ENSP00000419325.1	Q96I99-2
SUCLG2	ENST00000460567.5 link	c.412C>T	p.Arg138Trp	missense_variant	Exon 4 of 5	1		ENSP00000417260.1	H0Y852

Frequencies

GnomAD3 genomes

AF:

0.0535

AC:

8131

AN:

152066

Hom.:

688

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0222

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.0455

GnomAD2 exomes

AF:

0.0134

AC:

3336

AN:

248414

AF XY:

0.0102

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.00800

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000717

Gnomad OTH exome

AF:

0.00747

GnomAD4 exome

AF:

0.00561

AC:

8184

AN:

1459604

Hom.:

640

Cov.:

AF XY:

0.00494

AC XY:

3587

AN XY:

726190

show subpopulations

African (AFR)

AF:

0.189

AC:

6318

AN:

33350

American (AMR)

AF:

0.0100

AC:

446

AN:

44420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39614

South Asian (SAS)

AF:

0.000511

AC:

AN:

86074

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00950

AC:

AN:

4524

European-Non Finnish (NFE)

AF:

0.000505

AC:

561

AN:

1111856

Other (OTH)

AF:

0.0128

AC:

771

AN:

60220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

347

694

1040

1387

1734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

392

588

784

980

<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:

0.0535

AC:

8143

AN:

152184

Hom.:

691

Cov.:

AF XY:

0.0527

AC XY:

3920

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.185

AC:

7655

AN:

41490

American (AMR)

AF:

0.0221

AC:

338

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000831

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000691

AC:

AN:

68026

Other (OTH)

AF:

0.0451

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

333

666

1000

1333

1666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0189

Hom.:

529

Bravo

AF:

0.0616

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.173

AC:

674

ESP6500EA

AF:

0.000724

AC:

ExAC

AF:

0.0160

AC:

1935

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.000982

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 02, 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

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

.;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

M;M

PhyloP100

2.0

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-5.1

D;D

REVEL

Benign

0.22

Sift

Benign

0.057

T;D

Sift4G

Uncertain

0.023

D;D

Polyphen

0.032

.;B

Vest4

0.18

MPC

0.055

ClinPred

0.075

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.61

gMVP

0.76

Mutation Taster

=88/12

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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