Genetic Variant SUCLG1:c.98-11delT (chr2-84449762-TA-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.98-11delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 34 hom., cov: 0)

Exomes 𝑓: 0.0052 ( 1 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-TA-T is Benign according to our data. Variant chr2-84449762-TA-T is described in ClinVar as [Benign]. Clinvar id is 1244208.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCLG1	NM_003849.4 link	c.98-11delT		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.98-11delT		intron_variant	Intron 1 of 8	1	NM_003849.4	ENSP00000377446.2		P53597

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

1931

AN:

90030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0719

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000426

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00943

Gnomad NFE

AF:

0.000630

Gnomad OTH

AF:

0.0181

GnomAD4 exome

AF:

0.00519

AC:

3621

AN:

697062

Hom.:

Cov.:

AF XY:

0.00503

AC XY:

1826

AN XY:

362678

show subpopulations

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

African (AFR)

AF:

0.0187

AC:

286

AN:

15298

American (AMR)

AF:

0.00302

AC:

AN:

19536

Ashkenazi Jewish (ASJ)

AF:

0.00172

AC:

AN:

16264

East Asian (EAS)

AF:

0.000982

AC:

AN:

29540

South Asian (SAS)

AF:

0.00196

AC:

AN:

46914

European-Finnish (FIN)

AF:

0.00276

AC:

109

AN:

39500

Middle Eastern (MID)

AF:

0.00441

AC:

AN:

2266

European-Non Finnish (NFE)

AF:

0.00570

AC:

2827

AN:

495918

Other (OTH)

AF:

0.00569

AC:

181

AN:

31826

⚠️ 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: 0.285

Heterozygous variant carriers

305

610

916

1221

1526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

192

288

384

480

<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:

0.0214

AC:

1929

AN:

90034

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

890

AN XY:

41526

show subpopulations

African (AFR)

AF:

0.0718

AC:

1791

AN:

24952

American (AMR)

AF:

0.0103

AC:

AN:

8356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2408

East Asian (EAS)

AF:

0.00

AC:

AN:

2968

South Asian (SAS)

AF:

0.000429

AC:

AN:

2330

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2618

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

194

European-Non Finnish (NFE)

AF:

0.000630

AC:

AN:

44412

Other (OTH)

AF:

0.0179

AC:

AN:

1174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

146

219

292

365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00

Hom.:

848

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 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-TAAAAAAAAAAAAAAA

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