Genetic Variant SUCLG1:c.98-12_98-11dupTT (chr2-84449762-T-TAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003849.4(SUCLG1):c.98-12_98-11dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000011 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

SUCLG1
NM_003849.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCLG1	NM_003849.4 link	c.98-12_98-11dupTT		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.98-11_98-10insTT		intron_variant	Intron 1 of 8	1	NM_003849.4	ENSP00000377446.2		P53597

Frequencies

GnomAD3 genomes

AF:

0.0000111

AC:

AN:

90116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000120

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000627

AC:

AN:

701926

Hom.:

Cov.:

AF XY:

0.0000575

AC XY:

AN XY:

365294

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

15586

American (AMR)

AF:

0.0000508

AC:

AN:

19688

Ashkenazi Jewish (ASJ)

AF:

0.000123

AC:

AN:

16312

East Asian (EAS)

AF:

0.00

AC:

AN:

29662

South Asian (SAS)

AF:

0.0000847

AC:

AN:

47246

European-Finnish (FIN)

AF:

0.0000252

AC:

AN:

39682

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2280

European-Non Finnish (NFE)

AF:

0.0000641

AC:

AN:

499384

Other (OTH)

AF:

0.000125

AC:

AN:

32086

⚠️ 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: 0.309

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000111

AC:

AN:

90116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

41562

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

24994

American (AMR)

AF:

0.000120

AC:

AN:

8356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2410

East Asian (EAS)

AF:

0.00

AC:

AN:

2972

South Asian (SAS)

AF:

0.00

AC:

AN:

2346

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

44424

Other (OTH)

AF:

0.00

AC:

AN:

1162

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.061

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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2-84449762-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over