rs748090019
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_016004.5(IFT52):c.424C>T(p.Arg142Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,206 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
IFT52
NM_016004.5 stop_gained
NM_016004.5 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 1.89
Genes affected
IFT52 (HGNC:15901): (intraflagellar transport 52) This gene encodes a conserved proline-rich protein that is a component of the intraflagellar transport-B (IFT-B) core complex. The encoded protein is essential for the integrity of the IFT-B core complex, and for biosynthesis and maintenance of cilia. Mutations in this gene are associated with ciliopathy that affects the skeleton. [provided by RefSeq, Oct 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 20-43605012-C-T is Pathogenic according to our data. Variant chr20-43605012-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 253306.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFT52 | NM_016004.5 | c.424C>T | p.Arg142Ter | stop_gained | 6/14 | ENST00000373030.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFT52 | ENST00000373030.8 | c.424C>T | p.Arg142Ter | stop_gained | 6/14 | 1 | NM_016004.5 | P1 | |
IFT52 | ENST00000373039.4 | c.424C>T | p.Arg142Ter | stop_gained | 6/14 | 5 | P1 | ||
IFT52 | ENST00000476986.1 | n.103C>T | non_coding_transcript_exon_variant | 3/3 | 5 | ||||
IFT52 | ENST00000486243.1 | n.195C>T | non_coding_transcript_exon_variant | 3/3 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152066Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251132Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135744
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1461140Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 726888
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Short-rib thoracic dysplasia 16 with or without polydactyly Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 02, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at