2-218660069-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The ENST00000392109.5(BCS1L):c.-199A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 152,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
BCS1L
ENST00000392109.5 5_prime_UTR
ENST00000392109.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.368
Genes affected
BCS1L (HGNC:1020): (BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone) This gene encodes a homolog of the S. cerevisiae bcs1 protein which is involved in the assembly of complex III of the mitochondrial respiratory chain. The encoded protein does not contain a mitochondrial targeting sequence but experimental studies confirm that it is imported into mitochondria. Mutations in this gene are associated with mitochondrial complex III deficiency and the GRACILE syndrome. Several alternatively spliced transcripts encoding two different isoforms have been described. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 2-218660069-A-G is Pathogenic according to our data. Variant chr2-218660069-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2680147.Status of the report is criteria_provided_single_submitter, 1 stars.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).. Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCS1L | NM_001079866.2 | c.-50+326A>G | intron_variant | ENST00000359273.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCS1L | ENST00000359273.8 | c.-50+326A>G | intron_variant | 1 | NM_001079866.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152166Hom.: 0 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 34Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 20
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74328
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pili torti-deafness syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 16, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at