rs587777087
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015662.3(IFT172):c.3907C>T(p.Arg1303Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000109 in 1,461,888 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: not found (cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
IFT172
NM_015662.3 stop_gained
NM_015662.3 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 5.38
Genes affected
IFT172 (HGNC:30391): (intraflagellar transport 172) This gene encodes a subunit of the intraflagellar transport subcomplex IFT-B. Subcomplexes IFT-A and IFT-B are necessary for ciliary assembly and maintenance. Mutations in this gene have been associated with skeletal ciliopathies, with or without polydactyly, such as such short-rib thoracic dysplasias 1, 9 or 10. [provided by RefSeq, Mar 2014]
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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 2-27453428-G-A is Pathogenic according to our data. Variant chr2-27453428-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 97033.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-27453428-G-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFT172 | NM_015662.3 | c.3907C>T | p.Arg1303Ter | stop_gained | 35/48 | ENST00000260570.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFT172 | ENST00000260570.8 | c.3907C>T | p.Arg1303Ter | stop_gained | 35/48 | 1 | NM_015662.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251462Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135910
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461888Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 8AN XY: 727244
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GnomAD4 genome ? Cov.: 32
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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 10 with or without polydactyly;C4225342:Retinitis pigmentosa 71 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 07, 2022 | This sequence change creates a premature translational stop signal (p.Arg1303*) in the IFT172 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IFT172 are known to be pathogenic (PMID: 24140113). This variant is present in population databases (rs587777087, gnomAD 0.006%). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 97033). This premature translational stop signal has been observed in individual(s) with asphyxiating thoracic dystrophy (PMID: 24140113). - |
Short-rib thoracic dysplasia 10 with polydactyly Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 07, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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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