rs6561424

Variant names:

Variant summary

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

The NM_003850.3(SUCLA2):c.371+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,610,790 control chromosomes in the GnomAD database, including 503,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 41387 hom., cov: 33)

Exomes 𝑓: 0.79 ( 462492 hom. )

Consequence

SUCLA2
NM_003850.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.800

Publications

17 publications found

Variant links:

Genes affected

SUCLA2 (HGNC:11448): (succinate-CoA ligase ADP-forming subunit beta) Succinyl-CoA synthetase (SCS) is a mitochondrial matrix enzyme that acts as a heterodimer, being composed of an invariant alpha subunit and a substrate-specific beta subunit. The protein encoded by this gene is an ATP-specific SCS beta subunit that dimerizes with the SCS alpha subunit to form SCS-A, an essential component of the tricarboxylic acid cycle. SCS-A hydrolyzes ATP to convert succinate to succinyl-CoA. Defects in this gene are a cause of myopathic mitochondrial DNA depletion syndrome. A pseudogene of this gene has been found on chromosome 6. [provided by RefSeq, Jul 2008]

SUCLA2 Gene-Disease associations (from GenCC):

Leigh syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria
Inheritance: Mitochondrial, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

SUCLA2 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 (BayesDel_noAF=-0.84).

BP6

Variant 13-47988873-G-A is Benign according to our data. Variant chr13-47988873-G-A is described in ClinVar as Benign. ClinVar VariationId is 139358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCLA2	NM_003850.3 link	c.371+9C>T		intron_variant	Intron 3 of 10	ENST00000646932.1	NP_003841.1	Q9P2R7-1E5KS60Q9Y4T0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLA2	ENST00000646932.1 link	c.371+9C>T		intron_variant	Intron 3 of 10		NM_003850.3	ENSP00000494360.1		Q9P2R7-1

Frequencies

GnomAD3 genomes

AF:

0.730

AC:

110878

AN:

151976

Hom.:

41382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.584

Gnomad AMI

AF:

0.919

Gnomad AMR

AF:

0.676

Gnomad ASJ

AF:

0.796

Gnomad EAS

AF:

0.798

Gnomad SAS

AF:

0.623

Gnomad FIN

AF:

0.797

Gnomad MID

AF:

0.750

Gnomad NFE

AF:

0.815

Gnomad OTH

AF:

0.761

GnomAD2 exomes

AF:

0.748

AC:

187378

AN:

250556

AF XY:

0.750

show subpopulations

Gnomad AFR exome

AF:

0.581

Gnomad AMR exome

AF:

0.635

Gnomad ASJ exome

AF:

0.780

Gnomad EAS exome

AF:

0.792

Gnomad FIN exome

AF:

0.792

Gnomad NFE exome

AF:

0.818

Gnomad OTH exome

AF:

0.761

GnomAD4 exome

AF:

0.793

AC:

1157108

AN:

1458696

Hom.:

462492

Cov.:

AF XY:

0.789

AC XY:

572835

AN XY:

725764

show subpopulations

African (AFR)

AF:

0.571

AC:

19052

AN:

33394

American (AMR)

AF:

0.638

AC:

28502

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.783

AC:

20442

AN:

26122

East Asian (EAS)

AF:

0.780

AC:

30908

AN:

39638

South Asian (SAS)

AF:

0.636

AC:

54781

AN:

86114

European-Finnish (FIN)

AF:

0.791

AC:

41930

AN:

52998

Middle Eastern (MID)

AF:

0.726

AC:

3286

AN:

4528

European-Non Finnish (NFE)

AF:

0.820

AC:

911038

AN:

1111004

Other (OTH)

AF:

0.784

AC:

47169

AN:

60190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

11945

23891

35836

47782

59727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20782

41564

62346

83128

103910

<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:

0.729

AC:

110913

AN:

152094

Hom.:

41387

Cov.:

AF XY:

0.728

AC XY:

54104

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.583

AC:

24166

AN:

41440

American (AMR)

AF:

0.675

AC:

10316

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.796

AC:

2765

AN:

3472

East Asian (EAS)

AF:

0.797

AC:

4131

AN:

5180

South Asian (SAS)

AF:

0.623

AC:

3002

AN:

4818

European-Finnish (FIN)

AF:

0.797

AC:

8444

AN:

10590

Middle Eastern (MID)

AF:

0.745

AC:

219

AN:

294

European-Non Finnish (NFE)

AF:

0.815

AC:

55424

AN:

68000

Other (OTH)

AF:

0.761

AC:

1608

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1471

2943

4414

5886

7357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

840

1680

2520

3360

4200

<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:

0.778

Hom.:

27377

Bravo

AF:

0.715

Asia WGS

AF:

0.689

AC:

2392

AN:

3476

EpiCase

AF:

0.809

EpiControl

AF:

0.806

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 30, 2011

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

May 21, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 19, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 20, 2017

Athena Diagnostics

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

- -

Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria

Benign:3

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.9

(source)

DANN

Benign

0.64

PhyloP100

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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