2-84449762-TAAAAAAAAAAAAAAAA-TAAAA

Variant names:

• chr2-84449762-TAAAAAAAAAAAA-T
• rs56733272
• NM_003849.4:c.98-22_98-11delTTTTTTTTTTTT

Variant summary

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

The NM_003849.4(SUCLG1):​c.98-22_98-11delTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 701,978 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: SUCLG1 NM_003849.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71
• Publications: 3 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet, PanelApp Australia
• 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.98-22_98-11delTTTTTTTTTTTT		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.98-22_98-11delTTTTTTTTTTTT		intron	N/A	ENSP00000377446.2	P53597
	SUCLG1	ENST00000949558.1		c.98-22_98-11delTTTTTTTTTTTT		intron	N/A	ENSP00000619617.1
	SUCLG1	ENST00000912793.1		c.98-22_98-11delTTTTTTTTTTTT		intron	N/A	ENSP00000582852.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000171 AC: 12 AN: 701978 Hom.: 0 AF XY: 0.0000301 AC XY: 11 AN XY: 365318

⚠️ 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: 0.0000337 AC: 1 AN: 29662

South Asian (SAS) AF: 0.0000423 AC: 2 AN: 47252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39680

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

European-Non Finnish (NFE) AF: 0.0000140 AC: 7 AN: 499428

Other (OTH) AF: 0.0000623 AC: 2 AN: 32088

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0381496), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 848

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

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;