chr7-30014800-CTTT-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PM4_SupportingBP6
The NM_017946.4(FKBP14):c.568_570del(p.Lys190del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000337 in 1,611,602 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. K190K) has been classified as Likely benign.
Frequency
Consequence
NM_017946.4 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FKBP14 | NM_017946.4 | c.568_570del | p.Lys190del | inframe_deletion | 4/4 | ENST00000222803.10 | |
FKBP14 | XM_047420550.1 | c.477+4193_477+4195del | intron_variant | ||||
FKBP14 | NR_046478.2 | n.854_856del | non_coding_transcript_exon_variant | 5/5 | |||
FKBP14 | NR_046479.2 | n.610_612del | non_coding_transcript_exon_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FKBP14 | ENST00000222803.10 | c.568_570del | p.Lys190del | inframe_deletion | 4/4 | 1 | NM_017946.4 | P1 | |
FKBP14-AS1 | ENST00000422239.6 | n.679+6424_679+6426del | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000368 AC: 56AN: 152138Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000652 AC: 161AN: 247120Hom.: 0 AF XY: 0.000672 AC XY: 90AN XY: 133956
GnomAD4 exome AF: 0.000334 AC: 487AN: 1459346Hom.: 4 AF XY: 0.000351 AC XY: 255AN XY: 726108
GnomAD4 genome ? AF: 0.000368 AC: 56AN: 152256Hom.: 1 Cov.: 32 AF XY: 0.000296 AC XY: 22AN XY: 74444
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 27, 2019 | This observation is not an independent occurrence and has been identified in the same individual by RCIGM, the other laboratory participating in the GEMINI study. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 23, 2022 | Observed in the homozygous and compound heterozygous states in patients with arthrogryposis; however, features specific to kEDS, such as congenital hypotonia and kyphoscoliosis, were not reported (Greenbaum et al. 2019; Maron et al., 2021); In-frame deletion of one amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24677762, 24773188, 27149304, 22265013, 31428121, 34682862, 33587123) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 11, 2022 | BS1 - |
Ehlers-Danlos syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Aug 10, 2020 | - - |
Ehlers-Danlos syndrome, kyphoscoliotic type, 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 21, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at