chr7-30014872-CCTT-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PM4_SupportingBP6BS1BS2
The NM_017946.4(FKBP14):c.496_498delAAG(p.Lys166del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00136 in 1,594,244 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_017946.4 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FKBP14 | NM_017946.4 | c.496_498delAAG | p.Lys166del | conservative_inframe_deletion | Exon 4 of 4 | ENST00000222803.10 | NP_060416.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000986 AC: 150AN: 152074Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000998 AC: 229AN: 229478Hom.: 2 AF XY: 0.00116 AC XY: 145AN XY: 124498
GnomAD4 exome AF: 0.00140 AC: 2015AN: 1442052Hom.: 7 AF XY: 0.00143 AC XY: 1027AN XY: 717198
GnomAD4 genome AF: 0.000986 AC: 150AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.000968 AC XY: 72AN XY: 74414
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
FKBP14: PM4:Supporting, BS2 -
See Variant Classification Assertion Criteria. -
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Cardiovascular phenotype Uncertain:1
The c.496_498delAAG variant (also known as p.K166del), located in coding exon 4 of the FKBP14 gene, results from an in-frame AAG deletion at nucleotide positions 496 to 498. This results in the in-frame deletion of a lysine at codon 166. This variant was reported in one heterozygous individual from a cervical insufficiency cohort (Volozonoka L et al. PLoS One, 2020 Mar;15:e0230771). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Ehlers-Danlos syndrome Benign:1
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Ehlers-Danlos syndrome, kyphoscoliotic type, 2 Benign:1
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FKBP14-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at