Genetic Variant SUCLG1:c.98-12_98-11delTT (chr2-84449762-TAA-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_003849.4(SUCLG1):c.98-12_98-11delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 772,316 control chromosomes in the GnomAD database, including 322 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.060 ( 300 hom., cov: 0)

Exomes 𝑓: 0.029 ( 22 hom. )

Consequence

SUCLG1
NM_003849.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0610

Publications

3 publications found

Variant links:

Genes affected

SUCLG1 (HGNC:11449): (succinate-CoA ligase GDP/ADP-forming subunit alpha) This gene encodes the alpha subunit of the heterodimeric enzyme succinate coenzyme A ligase. This enzyme is targeted to the mitochondria and catalyzes the conversion of succinyl CoA and ADP or GDP to succinate and ATP or GTP. Mutations in this gene are the cause of the metabolic disorder fatal infantile lactic acidosis and mitochondrial DNA depletion. [provided by RefSeq, Feb 2010]

SUCLG1 Gene-Disease associations (from GenCC):

mitochondrial DNA depletion syndrome 9
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
Leigh syndrome
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

SUCLG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 2-84449762-TAA-T is Benign according to our data. Variant chr2-84449762-TAA-T is described in ClinVar as [Benign]. Clinvar id is 1296460.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCLG1	NM_003849.4 link	c.98-12_98-11delTT		intron_variant	Intron 1 of 8	ENST00000393868.7	NP_003840.2	P53597

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLG1	ENST00000393868.7 link	c.98-12_98-11delTT		intron_variant	Intron 1 of 8	1	NM_003849.4	ENSP00000377446.2		P53597

Frequencies

GnomAD3 genomes

AF:

0.0598

AC:

5379

AN:

89970

Hom.:

300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.00249

Gnomad EAS

AF:

0.0697

Gnomad SAS

AF:

0.0107

Gnomad FIN

AF:

0.0141

Gnomad MID

AF:

0.0142

Gnomad NFE

AF:

0.00557

Gnomad OTH

AF:

0.0500

GnomAD4 exome

AF:

0.0289

AC:

19724

AN:

682338

Hom.:

AF XY:

0.0279

AC XY:

9910

AN XY:

354678

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0844

AC:

1260

AN:

14934

American (AMR)

AF:

0.0229

AC:

432

AN:

18854

Ashkenazi Jewish (ASJ)

AF:

0.0193

AC:

307

AN:

15876

East Asian (EAS)

AF:

0.0270

AC:

774

AN:

28628

South Asian (SAS)

AF:

0.0217

AC:

973

AN:

44764

European-Finnish (FIN)

AF:

0.0167

AC:

649

AN:

38872

Middle Eastern (MID)

AF:

0.0332

AC:

AN:

2228

European-Non Finnish (NFE)

AF:

0.0295

AC:

14350

AN:

487024

Other (OTH)

AF:

0.0290

AC:

905

AN:

31158

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.288

Heterozygous variant carriers

1737

3475

5212

6950

8687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.0598

AC:

5382

AN:

89978

Hom.:

300

Cov.:

AF XY:

0.0608

AC XY:

2522

AN XY:

41502

show subpopulations

African (AFR)

AF:

0.184

AC:

4600

AN:

24956

American (AMR)

AF:

0.0239

AC:

200

AN:

8356

Ashkenazi Jewish (ASJ)

AF:

0.00249

AC:

AN:

2410

East Asian (EAS)

AF:

0.0695

AC:

206

AN:

2964

South Asian (SAS)

AF:

0.0107

AC:

AN:

2330

European-Finnish (FIN)

AF:

0.0141

AC:

AN:

2618

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

194

European-Non Finnish (NFE)

AF:

0.00557

AC:

247

AN:

44356

Other (OTH)

AF:

0.0503

AC:

AN:

1172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

185

370

556

741

926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.00569

Hom.:

848

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 23, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.061

Mutation Taster

=100/0

polymorphism

(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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2-84449762-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAA

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