rs1441549097
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Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5
The NM_014714.4(IFT140):āc.985T>Cā(p.Cys329Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,610,208 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 (no stars).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 6.9e-7 ( 0 hom. )
Consequence
IFT140
NM_014714.4 missense
NM_014714.4 missense
Scores
6
10
3
Clinical Significance
Conservation
PhyloP100: 8.90
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 Likely_pathogenic. Variant got 7 ACMG points.
PM1
In a repeat WD 7 (size 39) in uniprot entity IF140_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_014714.4
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.898
PP5
Variant 16-1587222-A-G is Pathogenic according to our data. Variant chr16-1587222-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 446313.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr16-1587222-A-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IFT140 | NM_014714.4 | c.985T>C | p.Cys329Arg | missense_variant | 9/31 | ENST00000426508.7 | NP_055529.2 | |
LOC105371046 | NR_135176.1 | n.59+6637A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IFT140 | ENST00000426508.7 | c.985T>C | p.Cys329Arg | missense_variant | 9/31 | 5 | NM_014714.4 | ENSP00000406012 | P1 | |
ENST00000563162.1 | n.59+6637A>G | intron_variant, non_coding_transcript_variant | 2 | |||||||
IFT140 | ENST00000439987.6 | n.1046T>C | non_coding_transcript_exon_variant | 8/19 | 2 | |||||
IFT140 | ENST00000397417.6 | c.329-2802T>C | intron_variant, NMD_transcript_variant | 5 | ENSP00000380562 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251408Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135904
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GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1458018Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1AN XY: 725696
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74358
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Retinitis pigmentosa 80 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 22, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Gain of MoRF binding (P = 0.0075);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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