2-74135948-C-CTT

Position:

• chr2-74135948-C-CTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_212552.3(BOLA3):​c.259-291_259-290insAA 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.489

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-74135948-C-CTT is Benign according to our data. Variant chr2-74135948-C-CTT is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BOLA3	NM_212552.3	c.259-291_259-290insAA		intron_variant		ENST00000327428.10	NP_997717.2
BOLA3	NM_001035505.2	c.170-291_170-290insAA		intron_variant			NP_001030582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BOLA3	ENST00000327428.10	c.259-291_259-290insAA		intron_variant		1	NM_212552.3	ENSP00000331369	P1

Frequencies

GnomAD3 genomes AF: 0.0457 AC: 6148 AN: 134606 Hom.: 337 Cov.: 0

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.: 0 AF XY: 0.0469 AC XY: 3012 AN XY: 64254

Gnomad4 AFR AF: 0.0752

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.00786

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.0111

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.0424

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 18, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs55654893; hg19: chr2-74363075;