chr17-41813048-G-GC
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_021939.4(FKBP10):c.21dup(p.Ser8GlnfsTer67) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000823 in 1,457,346 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G5G) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
FKBP10
NM_021939.4 frameshift
NM_021939.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.458
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]
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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
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Variant 17-41813048-G-GC is Pathogenic according to our data. Variant chr17-41813048-G-GC is described in ClinVar as [Pathogenic]. Clinvar id is 1457018.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.21dup | p.Ser8GlnfsTer67 | frameshift_variant | 1/10 | ENST00000321562.9 | |
FKBP10 | XM_011525099.4 | c.21dup | p.Ser8GlnfsTer67 | frameshift_variant | 1/11 | ||
FKBP10 | XM_011525100.3 | c.-107dup | 5_prime_UTR_variant | 1/10 | |||
FKBP10 | XM_047436515.1 | c.-107dup | 5_prime_UTR_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FKBP10 | ENST00000321562.9 | c.21dup | p.Ser8GlnfsTer67 | frameshift_variant | 1/10 | 1 | NM_021939.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 1AN: 152054Hom.: 0 Cov.: 32 FAILED QC
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GnomAD4 exome AF: 0.00000823 AC: 12AN: 1457346Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3AN XY: 724968
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1AN: 152054Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74280
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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 | Nov 05, 2023 | This sequence change creates a premature translational stop signal (p.Ser8Glnfs*67) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with osteogenesis imperfecta (PMID: 23613367). ClinVar contains an entry for this variant (Variation ID: 1457018). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at