chr2-74135948-C-CTTTTTTTTT

Variant names:

• chr2-74135948-C-CTTTTTTTTT
• rs55654893
• NM_212552.3:c.259-299_259-291dupAAAAAAAAA

Variant summary

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

The NM_212552.3(BOLA3):​c.259-299_259-291dupAAAAAAAAA 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 0.0000074 (0 hom., cov: 0)
• Consequence: BOLA3 NM_212552.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489
• Publications: 0 publications found

Genes affected

BOLA3 (HGNC:24415): (bolA family member 3) This gene encodes a protein that plays an essential role in the production of iron-sulfur (Fe-S) clusters for the normal maturation of lipoate-containing 2-oxoacid dehydrogenases, and for the assembly of the mitochondrial respiratory chain complexes. Mutation in this gene has been associated with multiple mitochondrial dysfunctions syndrome-2. Two alternatively spliced transcript variants encoding different isoforms with distinct subcellular localization have been reported for this gene (PMID:21944046). [provided by RefSeq, Dec 2011]

BOLA3 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• multiple mitochondrial dysfunctions syndrome 2

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Genomics England PanelApp

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212552.3. 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
	BOLA3	NM_212552.3	MANE Select	c.259-299_259-291dupAAAAAAAAA		intron	N/A	NP_997717.2	Q53S33-1
	BOLA3	NM_001035505.2		c.170-299_170-291dupAAAAAAAAA		intron	N/A	NP_001030582.1	Q53S33-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BOLA3	ENST00000327428.10	TSL:1 MANE Select	c.259-291_259-290insAAAAAAAAA		intron	N/A	ENSP00000331369.5	Q53S33-1
	BOLA3	ENST00000295326.4	TSL:1	c.170-291_170-290insAAAAAAAAA		intron	N/A	ENSP00000295326.4	Q53S33-2
	BOLA3	ENST00000477685.5	TSL:1	n.410-291_410-290insAAAAAAAAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000742 AC: 1 AN: 134710 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: 0.0000158

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000742 AC: 1 AN: 134710 Hom.: 0 Cov.: 0 AF XY: 0.0000156 AC XY: 1 AN XY: 64296

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

African (AFR) AF: 0.00 AC: 0 AN: 36314

American (AMR) AF: 0.00 AC: 0 AN: 13076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3308

East Asian (EAS) AF: 0.00 AC: 0 AN: 4654

South Asian (SAS) AF: 0.00 AC: 0 AN: 4138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000158 AC: 1 AN: 63466

Other (OTH) AF: 0.00 AC: 0 AN: 1836

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49

Splicing

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

Other links and lift over

dbSNP: rs55654893; hg19: chr2-74363075;