rs75464253
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_173630.4(RTTN):c.1929+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,613,312 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0070 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00071 ( 14 hom. )
Consequence
RTTN
NM_173630.4 splice_donor_region, intron
NM_173630.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0001212
2
Clinical Significance
Conservation
PhyloP100: 0.276
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 18-70166059-C-T is Benign according to our data. Variant chr18-70166059-C-T is described in ClinVar as [Benign]. Clinvar id is 386678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-70166059-C-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00701 (1068/152334) while in subpopulation AFR AF= 0.0241 (1003/41558). AF 95% confidence interval is 0.0229. There are 9 homozygotes in gnomad4. There are 482 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTTN | NM_173630.4 | c.1929+3G>A | splice_donor_region_variant, intron_variant | ENST00000640769.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTTN | ENST00000640769.2 | c.1929+3G>A | splice_donor_region_variant, intron_variant | 2 | NM_173630.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00700 AC: 1066AN: 152218Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00178 AC: 442AN: 248602Hom.: 4 AF XY: 0.00125 AC XY: 169AN XY: 134866
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GnomAD4 exome AF: 0.000706 AC: 1031AN: 1460978Hom.: 14 Cov.: 30 AF XY: 0.000581 AC XY: 422AN XY: 726794
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GnomAD4 genome ? AF: 0.00701 AC: 1068AN: 152334Hom.: 9 Cov.: 32 AF XY: 0.00647 AC XY: 482AN XY: 74488
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 04, 2018 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 24, 2017 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at