rs10135645
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001329943.3(KIAA0586):āc.1230A>Gā(p.Gly410=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,519,682 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0097 ( 31 hom., cov: 32)
Exomes š: 0.00092 ( 27 hom. )
Consequence
KIAA0586
NM_001329943.3 synonymous
NM_001329943.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.614
Genes affected
KIAA0586 (HGNC:19960): (KIAA0586) This gene encodes a conserved centrosomal protein that functions in ciliogenesis and responds to hedgehog signaling. Mutations in this gene causes Joubert syndrome 23. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 14-58453450-A-G is Benign according to our data. Variant chr14-58453450-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 475439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-58453450-A-G is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.614 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00968 (1474/152318) while in subpopulation AFR AF= 0.0331 (1376/41568). AF 95% confidence interval is 0.0316. There are 31 homozygotes in gnomad4. There are 697 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 31 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIAA0586 | NM_001329943.3 | c.1230A>G | p.Gly410= | synonymous_variant | 9/31 | ENST00000652326.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIAA0586 | ENST00000652326.2 | c.1230A>G | p.Gly410= | synonymous_variant | 9/31 | NM_001329943.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00969 AC: 1475AN: 152200Hom.: 31 Cov.: 32
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GnomAD3 exomes AF: 0.00215 AC: 328AN: 152444Hom.: 8 AF XY: 0.00151 AC XY: 123AN XY: 81510
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GnomAD4 exome AF: 0.000924 AC: 1263AN: 1367364Hom.: 27 Cov.: 26 AF XY: 0.000767 AC XY: 518AN XY: 675034
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GnomAD4 genome ? AF: 0.00968 AC: 1474AN: 152318Hom.: 31 Cov.: 32 AF XY: 0.00936 AC XY: 697AN XY: 74490
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 20, 2021 | - - |
Joubert syndrome 23;C4225286:Short-rib thoracic dysplasia 14 with polydactyly Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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