2-84449762-TAAAAAAAAAAAAA-T

Variant names:

• chr2-84449762-TAAAAAAAAAAAAA-T
• rs56733272
• NM_003849.4:c.98-23_98-11delTTTTTTTTTTTTT

Variant summary

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

The NM_003849.4(SUCLG1):​c.98-23_98-11delTTTTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 792,090 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: 𝑓 0.000011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000031 (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), Orphanet, G2P
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

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	c.98-23_98-11delTTTTTTTTTTTTT		intron_variant	Intron 1 of 8	ENST00000393868.7	NP_003840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUCLG1	ENST00000393868.7	c.98-23_98-11delTTTTTTTTTTTTT		intron_variant	Intron 1 of 8	1	NM_003849.4	ENSP00000377446.2

Frequencies

GnomAD3 genomes AF: 0.0000111 AC: 1 AN: 90116 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: 0.0000225

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000313 AC: 22 AN: 701974 Hom.: 0 AF XY: 0.0000328 AC XY: 12 AN XY: 365316

African (AFR) AF: 0.0000642 AC: 1 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: 0.0000212 AC: 1 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: 0.0000380 AC: 19 AN: 499424

Other (OTH) AF: 0.0000312 AC: 1 AN: 32088

GnomAD4 genome AF: 0.0000111 AC: 1 AN: 90116 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 41562

African (AFR) AF: 0.00 AC: 0 AN: 24994

American (AMR) AF: 0.00 AC: 0 AN: 8356

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 2972

South Asian (SAS) AF: 0.00 AC: 0 AN: 2346

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 212

European-Non Finnish (NFE) AF: 0.0000225 AC: 1 AN: 44424

Other (OTH) AF: 0.00 AC: 0 AN: 1162

Alfa AF: 0.00 Hom.: 848

ClinVar

Not reported in ClinVar

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

Other links and lift over

dbSNP: rs56733272; hg19: chr2-84676886;