chr7-30014811-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_017946.4(FKBP14):c.560T>G(p.Ile187Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. I187I) has been classified as Likely benign.
Frequency
Consequence
NM_017946.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FKBP14 | NM_017946.4 | c.560T>G | p.Ile187Ser | missense_variant | 4/4 | ENST00000222803.10 | |
FKBP14 | XM_047420550.1 | c.477+4185T>G | intron_variant | ||||
FKBP14 | NR_046478.2 | n.846T>G | non_coding_transcript_exon_variant | 5/5 | |||
FKBP14 | NR_046479.2 | n.602T>G | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FKBP14 | ENST00000222803.10 | c.560T>G | p.Ile187Ser | missense_variant | 4/4 | 1 | NM_017946.4 | P1 | |
FKBP14-AS1 | ENST00000422239.6 | n.679+6434A>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246600Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133664
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1459350Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 726120
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, kyphoscoliotic type, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 26, 2021 | This sequence change replaces isoleucine with serine at codon 187 of the FKBP14 protein (p.Ile187Ser). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and serine. This variant is present in population databases (rs773564727, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with FKBP14-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 11, 2023 | The p.I187S variant (also known as c.560T>G), located in coding exon 4 of the FKBP14 gene, results from a T to G substitution at nucleotide position 560. The isoleucine at codon 187 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at