17-41813039-TC-T
Position:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_021939.4(FKBP10):c.9del(p.Ala4ArgfsTer155) variant causes a frameshift 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
FKBP10
NM_021939.4 frameshift
NM_021939.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.62
Genes affected
FKBP10 (HGNC:18169): (FKBP prolyl isomerase 10) The protein encoded by this gene belongs to the FKBP-type peptidyl-prolyl cis/trans isomerase (PPIase) family. This protein localizes to the endoplasmic reticulum and acts as a molecular chaperone. Alternatively spliced variants encoding different isoforms have been reported, but their biological validity has not been determined.[provided by RefSeq, Nov 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 41 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-41813039-TC-T is Pathogenic according to our data. Variant chr17-41813039-TC-T is described in ClinVar as [Pathogenic]. Clinvar id is 2031705.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FKBP10 | NM_021939.4 | c.9del | p.Ala4ArgfsTer155 | frameshift_variant | 1/10 | ENST00000321562.9 | |
FKBP10 | XM_011525099.4 | c.9del | p.Ala4ArgfsTer155 | frameshift_variant | 1/11 | ||
FKBP10 | XM_011525100.3 | c.-119del | 5_prime_UTR_variant | 1/10 | |||
FKBP10 | XM_047436515.1 | c.-119del | 5_prime_UTR_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FKBP10 | ENST00000321562.9 | c.9del | p.Ala4ArgfsTer155 | frameshift_variant | 1/10 | 1 | NM_021939.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
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 | Invitae | Sep 21, 2022 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with FKBP10-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala4Argfs*155) in the FKBP10 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FKBP10 are known to be pathogenic (PMID: 22689593, 22949511). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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
Publications
No publications associated with this variant yet.