NM_021939.4:c.-8_78delCAGGCACCATGTTCCCCGCGGGCCCCCCCAGCCACAGCCTCCTCCGGCTCCCCCTGCTGCAGTTGCTGCTACTGGTGGTGCAGGCC

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PP5_Moderate

The NM_021939.4(FKBP10):​c.-8_78delCAGGCACCATGTTCCCCGCGGGCCCCCCCAGCCACAGCCTCCTCCGGCTCCCCCTGCTGCAGTTGCTGCTACTGGTGGTGCAGGCC​(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

FKBP10
NM_021939.4 frameshift, start_lost

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.85

Publications

0 publications found
Variant links:
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]
FKBP10 Gene-Disease associations (from GenCC):
  • Bruck syndrome 1
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • osteogenesis imperfecta type 11
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Illumina
  • osteogenesis imperfecta type 3
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • osteogenesis imperfecta type 4
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • arthrogryposis-like syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • Bruck syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 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 55 pathogenic variants in the truncated region.
PP5
Variant 17-41813025-TCCAGGCACCATGTTCCCCGCGGGCCCCCCCAGCCACAGCCTCCTCCGGCTCCCCCTGCTGCAGTTGCTGCTACTGGTGGTGCAGGC-T is Pathogenic according to our data. Variant chr17-41813025-TCCAGGCACCATGTTCCCCGCGGGCCCCCCCAGCCACAGCCTCCTCCGGCTCCCCCTGCTGCAGTTGCTGCTACTGGTGGTGCAGGC-T is described in ClinVar as [Pathogenic]. Clinvar id is 871073.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FKBP10NM_021939.4 linkc.-8_78delCAGGCACCATGTTCCCCGCGGGCCCCCCCAGCCACAGCCTCCTCCGGCTCCCCCTGCTGCAGTTGCTGCTACTGGTGGTGCAGGCC p.Met1fs frameshift_variant, start_lost Exon 1 of 10 ENST00000321562.9 NP_068758.3 Q96AY3-1A0A024R1W3Q8NAG5Q658U4
FKBP10NM_021939.4 linkc.-8_78delCAGGCACCATGTTCCCCGCGGGCCCCCCCAGCCACAGCCTCCTCCGGCTCCCCCTGCTGCAGTTGCTGCTACTGGTGGTGCAGGCC 5_prime_UTR_variant Exon 1 of 10 ENST00000321562.9 NP_068758.3 Q96AY3-1A0A024R1W3Q8NAG5Q658U4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FKBP10ENST00000321562.9 linkc.-8_78delCAGGCACCATGTTCCCCGCGGGCCCCCCCAGCCACAGCCTCCTCCGGCTCCCCCTGCTGCAGTTGCTGCTACTGGTGGTGCAGGCC p.Met1fs frameshift_variant, start_lost Exon 1 of 10 1 NM_021939.4 ENSP00000317232.4 Q96AY3-1
FKBP10ENST00000321562.9 linkc.-8_78delCAGGCACCATGTTCCCCGCGGGCCCCCCCAGCCACAGCCTCCTCCGGCTCCCCCTGCTGCAGTTGCTGCTACTGGTGGTGCAGGCC 5_prime_UTR_variant Exon 1 of 10 1 NM_021939.4 ENSP00000317232.4 Q96AY3-1

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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
May 01, 2018
CeGaT Center for Human Genetics Tuebingen
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
2.9
Mutation Taster
=17/183
disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

hg19: chr17-39969277; API