chr17-6589776-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014804.3(KIAA0753):c.2786+3C>T 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 0.0000107 in 1,590,576 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000097 ( 0 hom. )
Consequence
KIAA0753
NM_014804.3 splice_donor_region, intron
NM_014804.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.0001067
2
Clinical Significance
Conservation
PhyloP100: 0.933
Genes affected
KIAA0753 (HGNC:29110): (KIAA0753) This gene encodes a subunit of a protein complex that regulates ciliogenesis and cilia maintenance. The encoded protein has also been shown to regulate centriolar duplication. Mutations in this gene cause an orofaciodigital syndrome and a form of Joubert syndrome in human patients. [provided by RefSeq, May 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIAA0753 | NM_014804.3 | c.2786+3C>T | splice_donor_region_variant, intron_variant | ENST00000361413.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIAA0753 | ENST00000361413.8 | c.2786+3C>T | splice_donor_region_variant, intron_variant | 1 | NM_014804.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000883 AC: 2AN: 226444Hom.: 0 AF XY: 0.0000162 AC XY: 2AN XY: 123228
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GnomAD4 exome AF: 0.00000973 AC: 14AN: 1438404Hom.: 0 Cov.: 30 AF XY: 0.00000838 AC XY: 6AN XY: 715650
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74336
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2022 | This sequence change falls in intron 18 of the KIAA0753 gene. It does not directly change the encoded amino acid sequence of the KIAA0753 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs771581575, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with KIAA0753-related conditions. ClinVar contains an entry for this variant (Variation ID: 1524184). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
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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