rs747353360
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_017946.4(FKBP14):c.197+5_197+8del variant causes a splice donor 5th base, intron change. The variant allele was found at a frequency of 0.0000195 in 1,593,242 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
FKBP14
NM_017946.4 splice_donor_5th_base, intron
NM_017946.4 splice_donor_5th_base, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.43
Genes affected
FKBP14 (HGNC:18625): (FKBP prolyl isomerase 14) The protein encoded by this gene is a member of the FK506-binding protein family of peptidyl-prolyl cis-trans isomerases. The encoded protein is found in the lumen of the endoplasmic reticulum, where it is thought to accelerate protein folding. Defects in this gene are a cause of a type of Ehlers-Danlos syndrome (EDS). Both a protein-coding variant and noncoding variants are transcribed from this gene. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 7-30026303-ATTAC-A is Pathogenic according to our data. Variant chr7-30026303-ATTAC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 161456.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-30026303-ATTAC-A is described in Lovd as [Pathogenic]. Variant chr7-30026303-ATTAC-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FKBP14 | NM_017946.4 | c.197+5_197+8del | splice_donor_5th_base_variant, intron_variant | ENST00000222803.10 | |||
FKBP14 | XM_047420550.1 | c.197+5_197+8del | splice_donor_5th_base_variant, intron_variant | ||||
FKBP14 | NR_046478.2 | n.391+5_391+8del | splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant | ||||
FKBP14 | NR_046479.2 | n.391+5_391+8del | splice_donor_5th_base_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FKBP14 | ENST00000222803.10 | c.197+5_197+8del | splice_donor_5th_base_variant, intron_variant | 1 | NM_017946.4 | P1 | |||
FKBP14-AS1 | ENST00000422239.6 | n.1601_1604del | non_coding_transcript_exon_variant | 4/4 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152226Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000577 AC: 14AN: 242522Hom.: 0 AF XY: 0.0000835 AC XY: 11AN XY: 131704
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GnomAD4 exome AF: 0.0000194 AC: 28AN: 1440898Hom.: 0 AF XY: 0.0000293 AC XY: 21AN XY: 716044
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152344Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74494
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Ehlers-Danlos syndrome, kyphoscoliotic type, 2 Pathogenic:3
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 26, 2024 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2014 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City | Oct 11, 2020 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -12
DS_DL_spliceai
Position offset: 9
Find out detailed SpliceAI scores and Pangolin per-transcript scores at