rs1555266475
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_014055.4(IFT81):c.1303_1305del(p.Leu435del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000481 in 1,455,762 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
IFT81
NM_014055.4 inframe_deletion
NM_014055.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.02
Genes affected
IFT81 (HGNC:14313): (intraflagellar transport 81) The protein encoded by this gene, together with IFT74, forms a tubulin-binding module of intraflagellar transport complex B. This module is involved in transport of tubulin within the cilium, and the encoded protein is required for ciliogenesis. Mutations in this gene are a cause of short-rib polydactyly syndromes. [provided by RefSeq, Dec 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_014055.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFT81 | NM_014055.4 | c.1303_1305del | p.Leu435del | inframe_deletion | 12/19 | ENST00000242591.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFT81 | ENST00000242591.10 | c.1303_1305del | p.Leu435del | inframe_deletion | 12/19 | 1 | NM_014055.4 | P1 | |
IFT81 | ENST00000552912.5 | c.1303_1305del | p.Leu435del | inframe_deletion | 12/19 | 1 | P1 | ||
IFT81 | ENST00000551055.1 | n.307_309del | non_coding_transcript_exon_variant | 2/3 | 3 | ||||
IFT81 | ENST00000550156.5 | c.1211_1213del | p.Leu405del | inframe_deletion, NMD_transcript_variant | 11/20 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000481 AC: 7AN: 1455762Hom.: 0 AF XY: 0.00000828 AC XY: 6AN XY: 724236
GnomAD4 exome
AF:
AC:
7
AN:
1455762
Hom.:
AF XY:
AC XY:
6
AN XY:
724236
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:2Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Short-rib thoracic dysplasia 19 with or without polydactyly Pathogenic:1Uncertain:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 28, 2018 | - - |
Uncertain significance, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Oct 15, 2018 | This variant is interpreted as Uncertain Significance - Insufficient Evidence, for Short-rib thoracic dysplasia 19 with or without polydactyly, autosomal recessive. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PM3 => For recessive disorders, detected in trans with a pathogenic variant (https://www.ncbi.nlm.nih.gov/pubmed/27666822). - |
Short rib-polydactyly syndrome Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at