rs121908573

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

Scores

6
9
4

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 6.71
Variant links:
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]

Genome browser will be placed here

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
BCS1LNM_001079866.2 linkuse as main transcriptc.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
BCS1LENST00000359273.8 linkuse as main transcriptc.464G>A p.Arg155Gln missense_variant 4/81 NM_001079866.2 ENSP00000352219 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250346
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135342
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000172
AC:
25
AN:
1456582
Hom.:
0
Cov.:
33
AF XY:
0.0000138
AC XY:
10
AN XY:
723442
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000217
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingBaylor GeneticsMar 03, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.66
D;D;.;D;D;D;D;D;D;D
Eigen
Uncertain
0.64
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.96
.;D;D;.;.;.;.;.;.;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.81
D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.76
D
MutationAssessor
Uncertain
2.0
.;.;.;M;M;M;M;M;M;M
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-2.5
N;N;D;D;D;D;D;D;D;D
REVEL
Pathogenic
0.72
Sift
Benign
0.081
T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.089
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
0.59
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
0.99
MPC
1.4
ClinPred
0.90
D
GERP RS
5.3
Varity_R
0.42
gMVP
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs121908573; hg19: chr2-219526485; COSMIC: COSV99829191; COSMIC: COSV99829191; API