2-84449762-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr2-84449762-T-TAAAAA
• rs56733272
• NM_003849.4:c.98-15_98-11dupTTTTT

Variant summary

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

The NM_003849.4(SUCLG1):​c.98-15_98-11dupTTTTT 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 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SUCLG1 NM_003849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 0 publications found

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: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003849.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLG1	NM_003849.4	MANE Select	c.98-15_98-11dupTTTTT		intron	N/A	NP_003840.2	P53597

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUCLG1	ENST00000393868.7	TSL:1 MANE Select	c.98-11_98-10insTTTTT		intron	N/A	ENSP00000377446.2	P53597
	SUCLG1	ENST00000949558.1		c.98-11_98-10insTTTTT		intron	N/A	ENSP00000619617.1
	SUCLG1	ENST00000912793.1		c.98-11_98-10insTTTTT		intron	N/A	ENSP00000582852.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 90112 Hom.: 0 Cov.: 0

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000142 AC: 1 AN: 701988 Hom.: 0 Cov.: 0 AF XY: 0.00000274 AC XY: 1 AN XY: 365326

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

African (AFR) AF: 0.00 AC: 0 AN: 15586

American (AMR) AF: 0.00 AC: 0 AN: 19690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16312

East Asian (EAS) AF: 0.00 AC: 0 AN: 29662

South Asian (SAS) AF: 0.00 AC: 0 AN: 47254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39682

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2280

European-Non Finnish (NFE) AF: 0.00000200 AC: 1 AN: 499434

Other (OTH) AF: 0.00 AC: 0 AN: 32088

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 90118 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 41572

African (AFR) AF: 0.00 AC: 0 AN: 25024

American (AMR) AF: 0.00 AC: 0 AN: 8362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2410

East Asian (EAS) AF: 0.00 AC: 0 AN: 2968

South Asian (SAS) AF: 0.00 AC: 0 AN: 2330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 192

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 44418

Other (OTH) AF: 0.00 AC: 0 AN: 1174

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.061

Splicing

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

Other links and lift over

dbSNP: rs56733272; hg19: chr2-84676886;