NM_212552.3:c.259-293_259-291delAAA

Variant names:

• chr2-74135948-CTTT-C
• rs55654893
• NM_212552.3:c.259-293_259-291delAAA

Variant summary

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

The NM_212552.3(BOLA3):​c.259-293_259-291delAAA 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 0.00010 (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: Genomics England PanelApp, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

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.259-293_259-291delAAA		intron	N/A	NP_997717.2	Q53S33-1
	BOLA3	NM_001035505.2		c.170-293_170-291delAAA		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.259-293_259-291delAAA		intron	N/A	ENSP00000331369.5	Q53S33-1
	BOLA3	ENST00000295326.4	TSL:1	c.170-293_170-291delAAA		intron	N/A	ENSP00000295326.4	Q53S33-2
	BOLA3	ENST00000477685.5	TSL:1	n.410-293_410-291delAAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000104 AC: 14 AN: 134694 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000551

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: 0.000739

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000110

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000104 AC: 14 AN: 134678 Hom.: 0 Cov.: 0 AF XY: 0.000124 AC XY: 8 AN XY: 64300

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

African (AFR) AF: 0.0000550 AC: 2 AN: 36358

American (AMR) AF: 0.00 AC: 0 AN: 13082

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4638

South Asian (SAS) AF: 0.00 AC: 0 AN: 4110

European-Finnish (FIN) AF: 0.000739 AC: 5 AN: 6770

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 254

European-Non Finnish (NFE) AF: 0.000110 AC: 7 AN: 63450

Other (OTH) AF: 0.00 AC: 0 AN: 1842

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000000122347), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs55654893; hg19: chr2-74363075;