Genetic Variant BOLA3:c.259-292_259-291dupAA (chr2-74135947-TC-TCTT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_212552.3(BOLA3):c.259-292_259-291dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.046 ( 337 hom., cov: 0)

Consequence

BOLA3
NM_212552.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.489

Publications

0 publications found

Variant links:

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)

BOLA3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 2-74135947-TC-TCTT is Benign according to our data. Variant chr2-74135948-C-CTT is described in ClinVar as Benign. ClinVar VariationId is 1274334.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

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.259-292_259-291dupAA		intron	N/A	NP_997717.2	Q53S33-1
	BOLA3	NM_001035505.2		c.170-292_170-291dupAA		intron	N/A	NP_001030582.1	Q53S33-2

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.0457

AC:

6148

AN:

134606

Hom.:

337

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0753

Gnomad AMI

AF:

0.00115

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.00786

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.0111

Gnomad MID

AF:

0.00719

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.0425

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

GnomAD4 genome

AF:

0.0456

AC:

6144

AN:

134592

Hom.:

337

Cov.:

AF XY:

0.0469

AC XY:

3012

AN XY:

64254

show subpopulations

African (AFR)

AF:

0.0752

AC:

2731

AN:

36308

American (AMR)

AF:

0.139

AC:

1810

AN:

13058

Ashkenazi Jewish (ASJ)

AF:

0.00786

AC:

AN:

3306

East Asian (EAS)

AF:

0.122

AC:

564

AN:

4628

South Asian (SAS)

AF:

0.0170

AC:

AN:

4110

European-Finnish (FIN)

AF:

0.0111

AC:

AN:

6770

Middle Eastern (MID)

AF:

0.00394

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.0124

AC:

788

AN:

63452

Other (OTH)

AF:

0.0424

AC:

AN:

1840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

227

454

682

909

1136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00475

Hom.:

183

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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.

Publications

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2-74135948-C-CTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over