Genetic Variant NM_003849.4:c.98-25_98-11delTTTTTTTTTTTTTTT (chr2-84449762-TAAAAAAAAAAAAAAA-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_003849.4(SUCLG1):c.98-25_98-11delTTTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 792,104 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000011 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

SUCLG1
NM_003849.4 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.71

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: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 2-84449762-TAAAAAAAAAAAAAAA-T is Benign according to our data. Variant chr2-84449762-TAAAAAAAAAAAAAAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1928472.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUCLG1	NM_003849.4 link	c.98-25_98-11delTTTTTTTTTTTTTTT		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.98-25_98-11delTTTTTTTTTTTTTTT		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:

0.00

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:

0.0000225

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

701988

Hom.:

AF XY:

0.0000192

AC XY:

AN XY:

365324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15586

American (AMR)

AF:

0.00

AC:

AN:

19690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16312

East Asian (EAS)

AF:

0.0000337

AC:

AN:

29662

South Asian (SAS)

AF:

0.0000635

AC:

AN:

47254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39682

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2280

European-Non Finnish (NFE)

AF:

0.0000160

AC:

AN:

499434

Other (OTH)

AF:

0.00

AC:

AN:

32088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000241

AC XY:

AN XY:

41562

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24994

American (AMR)

AF:

0.00

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:

0.0000225

AC:

AN:

44424

Other (OTH)

AF:

0.00

AC:

AN:

1162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

848

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Mitochondrial DNA depletion syndrome 9

Benign:1

Jul 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.7

Splicing

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over