rs397514422
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP5_Moderate
The NM_001370658.1(BTD):c.1399T>C(p.Trp467Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
BTD
NM_001370658.1 missense
NM_001370658.1 missense
Scores
1
4
7
Clinical Significance
Conservation
PhyloP100: 1.80
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 6 ACMG points.
PM1
?
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in NM_001370658.1
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-15645315-T-C is Pathogenic according to our data. Variant chr3-15645315-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 25091.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-15645315-T-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BTD | NM_001370658.1 | c.1399T>C | p.Trp467Arg | missense_variant | 4/4 | ENST00000643237.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BTD | ENST00000643237.3 | c.1399T>C | p.Trp467Arg | missense_variant | 4/4 | NM_001370658.1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 13, 2015 | The W487R missense variant in the BTD gene has been reported previously in association with biotinidasedeficiency (Pomponio et al., 2000; ARUP BTD mutation database). Furthermore, multiple missense variantsin nearby residues (A478P, G488D, N489T, P497S) have been reported in the Human Gene MutationDatabase in association with biotinidase deficiency (Stenson et al., 2014). We consider this variant to be pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Polyphen
0.044
.;.;B;.;.;.;.
Vest4
0.28, 0.29, 0.27
MutPred
0.89
.;.;Gain of sheet (P = 0.0028);.;.;.;.;
MVP
0.96
MPC
0.14
ClinPred
T
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