rs3783697
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001329943.3(KIAA0586):āc.3920A>Gā(p.Asp1307Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00616 in 1,550,530 control chromosomes in the GnomAD database, including 407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0092 ( 40 hom., cov: 32)
Exomes š: 0.0058 ( 367 hom. )
Consequence
KIAA0586
NM_001329943.3 missense
NM_001329943.3 missense
Scores
1
6
9
Clinical Significance
Conservation
PhyloP100: 7.00
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.002554804).
BP6
?
Variant 14-58492205-A-G is Benign according to our data. Variant chr14-58492205-A-G is described in ClinVar as [Benign]. Clinvar id is 475450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0875 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIAA0586 | NM_001329943.3 | c.3920A>G | p.Asp1307Gly | missense_variant | 26/31 | ENST00000652326.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIAA0586 | ENST00000652326.2 | c.3920A>G | p.Asp1307Gly | missense_variant | 26/31 | NM_001329943.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00925 AC: 1408AN: 152220Hom.: 40 Cov.: 32
GnomAD3 genomes
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32
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GnomAD3 exomes AF: 0.0243 AC: 3839AN: 157738Hom.: 199 AF XY: 0.0209 AC XY: 1743AN XY: 83284
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GnomAD4 exome AF: 0.00583 AC: 8147AN: 1398192Hom.: 367 Cov.: 30 AF XY: 0.00559 AC XY: 3857AN XY: 689646
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GnomAD4 genome ? AF: 0.00924 AC: 1407AN: 152338Hom.: 40 Cov.: 32 AF XY: 0.0104 AC XY: 777AN XY: 74514
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577
Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 20, 2018 | - - |
Joubert syndrome 23;C4225286:Short-rib thoracic dysplasia 14 with polydactyly Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D;D;D;.;D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;.;.;.;D;D
REVEL
Benign
Sift
Uncertain
D;.;.;.;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
0.96
.;.;.;D;.;.
Vest4
MPC
ClinPred
T
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