rs121908573
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The NM_001079866.2(BCS1L):c.464G>A(p.Arg155Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000172 in 1,456,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
BCS1L
NM_001079866.2 missense
NM_001079866.2 missense
Scores
6
9
4
Clinical Significance
Conservation
PhyloP100: 6.71
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 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.81
PP5
Variant 2-218661762-G-A is Pathogenic according to our data. Variant chr2-218661762-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3240922.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BCS1L | NM_001079866.2 | c.464G>A | p.Arg155Gln | missense_variant | 4/8 | ENST00000359273.8 | NP_001073335.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BCS1L | ENST00000359273.8 | c.464G>A | p.Arg155Gln | missense_variant | 4/8 | 1 | NM_001079866.2 | ENSP00000352219 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250346Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135342
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GnomAD4 exome AF: 0.0000172 AC: 25AN: 1456582Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10AN XY: 723442
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GnomAD4 genome Cov.: 33
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33
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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 | Mar 03, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D;.;D;D;D;D;D;D;D
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;.;.;.;.;.;.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;.;.;M;M;M;M;M;M;M
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;D;D;D;D;D;D;D;D
REVEL
Pathogenic
Sift
Benign
T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T
Polyphen
0.94
.;.;.;P;P;P;P;P;P;P
Vest4
0.76, 0.77, 0.77, 0.80, 0.79
MutPred
Gain of disorder (P = 0.123);Gain of disorder (P = 0.123);.;Gain of disorder (P = 0.123);Gain of disorder (P = 0.123);Gain of disorder (P = 0.123);Gain of disorder (P = 0.123);Gain of disorder (P = 0.123);Gain of disorder (P = 0.123);Gain of disorder (P = 0.123);
MVP
MPC
1.4
ClinPred
D
GERP RS
Varity_R
gMVP
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