rs1256028809
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_173630.4(RTTN):c.5648-5T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
RTTN
NM_173630.4 splice_region, splice_polypyrimidine_tract, intron
NM_173630.4 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.9685
1
1
Clinical Significance
Conservation
PhyloP100: 1.64
Genes affected
RTTN (HGNC:18654): (rotatin) This gene encodes a large protein whose specific function is unknown. Absence of the orthologous protein in mouse results in embryonic lethality with deficient axial rotation, abnormal differentiation of the neural tube, and randomized looping of the heart tube during development. In human, mutations in this gene are associated with polymicrogyria with seizures. In human fibroblasts this protein localizes at the ciliary basal bodies. Given the intracellular localization of this protein and the phenotypic effects of mutations, this gene is suspected of playing a role in the maintenance of normal ciliary structure which in turn effects the developmental process of left-right organ specification, axial rotation, and perhaps notochord development. [provided by RefSeq, Jan 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 18-70030114-A-T is Pathogenic according to our data. Variant chr18-70030114-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 562178.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RTTN | NM_173630.4 | c.5648-5T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000640769.2 | NP_775901.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RTTN | ENST00000640769.2 | c.5648-5T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 2 | NM_173630.4 | ENSP00000491507 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 247180Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134212
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GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1448738Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1AN XY: 721482
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GnomAD4 genome Cov.: 32
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32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Microcephalic primordial dwarfism due to RTTN deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Research Group Niklas Dahl, Uppsala University | Sep 03, 2018 | - - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -5
Find out detailed SpliceAI scores and Pangolin per-transcript scores at