rs200938488

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_StrongBS1

The NM_212552.3(BOLA3):​c.282G>C​(p.Glu94Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E94E) has been classified as Likely benign.

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000062 ( 0 hom. )

Consequence

BOLA3
NM_212552.3 missense

Scores

1
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.04
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]
TET3 (HGNC:28313): (tet methylcytosine dioxygenase 3) Enables methyl-CpG binding activity and zinc ion binding activity. Involved in histone H3-K4 trimethylation; positive regulation of transcription by RNA polymerase II; and protein O-linked glycosylation. Predicted to be located in cytoplasm and male pronucleus. Predicted to be active in nucleus. Biomarker of esophagus squamous cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.009950578).
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000263 (4/152270) while in subpopulation EAS AF= 0.000772 (4/5182). AF 95% confidence interval is 0.000263. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BOLA3NM_212552.3 linkc.282G>C p.Glu94Asp missense_variant Exon 4 of 4 ENST00000327428.10 NP_997717.2 Q53S33-1
BOLA3NM_001035505.2 linkc.193G>C p.Asp65His missense_variant Exon 3 of 3 NP_001030582.1 Q53S33-2Q8N338
TET3XM_024452745.2 linkc.*392C>G downstream_gene_variant XP_024308513.1
TET3XM_024452746.2 linkc.*392C>G downstream_gene_variant XP_024308514.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BOLA3ENST00000327428.10 linkc.282G>C p.Glu94Asp missense_variant Exon 4 of 4 1 NM_212552.3 ENSP00000331369.5 Q53S33-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152152
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000770
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251416
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000435
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461586
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727126
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000227
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152270
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000772
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000412
AC:
5
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
0.67
DANN
Benign
0.90
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.010
T
MetaSVM
Benign
-0.96
T
PROVEAN
Benign
5.2
N
REVEL
Benign
0.045
Sift
Uncertain
0.014
D
Sift4G
Benign
0.14
T
Vest4
0.20
MVP
0.17
ClinPred
0.030
T
GERP RS
-7.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200938488; hg19: chr2-74362762; API