chr7-30014800-CTTT-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_SupportingBS2
The NM_017946.4(FKBP14):c.568_570delAAA(p.Lys190del) variant causes a conservative 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).
Frequency
Consequence
NM_017946.4 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FKBP14 | NM_017946.4 | c.568_570delAAA | p.Lys190del | conservative_inframe_deletion | Exon 4 of 4 | ENST00000222803.10 | NP_060416.1 |
Ensembl
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 Pathogenic:1Uncertain:2
BS1 -
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 (PMID: 33587123, 31428121); In silico analysis supports a deleterious effect on protein structure/function; In-frame deletion of one amino acid in a non-repeat region; This variant is associated with the following publications: (PMID: 24677762, 24773188, 27149304, 22265013, 31428121, 34682862, 33587123, 37432431) -
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. -
Ehlers-Danlos syndrome Uncertain:1
- -
Ehlers-Danlos syndrome, kyphoscoliotic type, 2 Benign:1
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Cardiovascular phenotype Benign:1
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