rs1050035768
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_ModeratePP5_Moderate
The NM_001370658.1(BTD):c.1568A>G(p.Asp523Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D523E) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 32)
Consequence
BTD
NM_001370658.1 missense
NM_001370658.1 missense
Scores
10
5
4
Clinical Significance
Conservation
PhyloP100: 8.67
Genes affected
BTD (HGNC:1122): (biotinidase) The protein encoded by this gene functions to recycle protein-bound biotin by cleaving biocytin (biotin-epsilon-lysine), a normal product of carboxylase degradation, resulting in regeneration of free biotin. The encoded protein has also been shown to have biotinyl transferase activity. Mutations in this gene are associated with biotinidase deficiency. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Aug 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr3-15645485-C-A is described in Lovd as [Likely_pathogenic].
PP3
MetaRNN computational evidence supports a deleterious effect, 0.898
PP5
Variant 3-15645484-A-G is Pathogenic according to our data. Variant chr3-15645484-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 800903.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| BTD | NM_001370658.1 | c.1568A>G | p.Asp523Gly | missense_variant | Exon 4 of 4 | ENST00000643237.3 | NP_001357587.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Biotinidase deficiency Pathogenic:2
Sep 22, 2024
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Sep 26, 2019
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
Significance: Likely pathogenic
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
.;.;D;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;T;.;.;T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
.;.;M;.;.;.;.
PrimateAI
Benign
T
PROVEAN
Pathogenic
.;D;.;.;.;D;D
REVEL
Pathogenic
Sift
Uncertain
.;D;.;.;.;D;D
Sift4G
Pathogenic
.;D;.;.;.;D;D
Polyphen
1.0
.;.;D;.;.;.;.
Vest4
0.75, 0.77, 0.71
MutPred
0.73
.;.;Loss of stability (P = 0.0326);.;.;.;.;
MVP
0.95
MPC
0.40
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at