Variant rs377025174 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP4

The NM_001079866.2(BCS1L):c.205C>A(p.Arg69Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R69C) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BCS1L
NM_001079866.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.97

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]

BCS1L links:

BCS1L (HGNC:):

BCS1L links:

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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;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr2-218661192-C-T is described in Lovd as [Likely_pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.32694036).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCS1L	NM_001079866.2 linkuse as main transcript	c.205C>A	p.Arg69Ser	missense_variant	2/8	ENST00000359273.8	NP_001073335.1	Q9Y276A0A024R445

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCS1L	ENST00000359273.8 linkuse as main transcript	c.205C>A	p.Arg69Ser	missense_variant	2/8	1	NM_001079866.2	ENSP00000352219.3		Q9Y276

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251480

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135908

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

.;T;T;D;D;D;.;D;D;D;D;.

Eigen

Benign

-0.060

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.87

D;.;D;.;.;.;D;.;.;.;D;D

M_CAP

Benign

0.050

MetaRNN

Benign

0.33

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.27

MutationAssessor

Benign

1.3

.;.;.;L;L;L;.;L;L;L;L;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.92

N;N;N;N;N;N;N;N;N;N;N;.

REVEL

Uncertain

0.34

Sift

Benign

0.14

T;T;T;T;T;T;T;T;T;T;T;.

Sift4G

Benign

0.77

T;T;T;T;T;T;T;T;T;T;T;.

Polyphen

0.021

.;.;.;B;B;B;.;B;B;B;B;.

Vest4

0.40, 0.41, 0.40, 0.37, 0.37

MutPred

0.57

Loss of MoRF binding (P = 0.0089);Loss of MoRF binding (P = 0.0089);Loss of MoRF binding (P = 0.0089);Loss of MoRF binding (P = 0.0089);Loss of MoRF binding (P = 0.0089);Loss of MoRF binding (P = 0.0089);Loss of MoRF binding (P = 0.0089);Loss of MoRF binding (P = 0.0089);Loss of MoRF binding (P = 0.0089);Loss of MoRF binding (P = 0.0089);Loss of MoRF binding (P = 0.0089);Loss of MoRF binding (P = 0.0089);

MVP

0.99

MPC

0.79

ClinPred

0.42

GERP RS

5.5

Varity_R

0.28

gMVP

0.45

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over