rs1085307074
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_014714.4(IFT140):c.1167del(p.Lys390ArgfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R389R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
IFT140
NM_014714.4 frameshift
NM_014714.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.690
Genes affected
IFT140 (HGNC:29077): (intraflagellar transport 140) This gene encodes one of the subunits of the intraflagellar transport (IFT) complex A. Intraflagellar transport is involved in the genesis, resorption and signaling of primary cilia. The primary cilium is a microtubule-based sensory organelle at the surface of most quiescent mammalian cells, that receives signals from its environment, such as the flow of fluid, light or odors, and transduces those signals to the nucleus. Loss of the corresponding protein in mouse results in renal cystic disease. [provided by RefSeq, Jun 2012]
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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 16-1584408-TC-T is Pathogenic according to our data. Variant chr16-1584408-TC-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 225390.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFT140 | NM_014714.4 | c.1167del | p.Lys390ArgfsTer6 | frameshift_variant | 11/31 | ENST00000426508.7 | |
LOC105371046 | NR_135176.1 | n.59+3825del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFT140 | ENST00000426508.7 | c.1167del | p.Lys390ArgfsTer6 | frameshift_variant | 11/31 | 5 | NM_014714.4 | P1 | |
ENST00000563162.1 | n.59+3825del | intron_variant, non_coding_transcript_variant | 2 | ||||||
IFT140 | ENST00000439987.6 | n.1228del | non_coding_transcript_exon_variant | 10/19 | 2 | ||||
IFT140 | ENST00000397417.6 | c.340del | p.Glu114LysfsTer1036 | frameshift_variant, NMD_transcript_variant | 4/24 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Saldino-Mainzer syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
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