14-58427631-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The ENST00000619416.4(KIAA0586):c.-45G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000111 in 1,535,590 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 0.00018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
KIAA0586
ENST00000619416.4 5_prime_UTR
ENST00000619416.4 5_prime_UTR
Scores
1
1
12
Clinical Significance
Conservation
PhyloP100: 0.551
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26937157).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIAA0586 | NM_001244189.2 | c.3G>A | p.Met1? | start_lost | 1/34 | ||
KIAA0586 | NM_001244190.2 | c.-45G>A | 5_prime_UTR_variant | 1/32 | |||
KIAA0586 | NM_001244191.2 | c.-63G>A | 5_prime_UTR_variant | 1/31 | |||
KIAA0586 | NM_001244192.2 | c.-63G>A | 5_prime_UTR_variant | 1/32 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIAA0586 | ENST00000423743.7 | c.-63G>A | 5_prime_UTR_variant | 1/32 | 1 | ||||
KIAA0586 | ENST00000619416.4 | c.-45G>A | 5_prime_UTR_variant | 1/32 | 1 | A2 | |||
KIAA0586 | ENST00000354386.10 | c.3G>A | p.Met1? | start_lost | 1/34 | 2 | |||
KIAA0586 | ENST00000619722.5 | c.-63G>A | 5_prime_UTR_variant | 1/31 | 2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000184 AC: 28AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000224 AC: 29AN: 129466Hom.: 0 AF XY: 0.000169 AC XY: 12AN XY: 70840
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GnomAD4 exome AF: 0.000103 AC: 142AN: 1383376Hom.: 0 Cov.: 30 AF XY: 0.0000894 AC XY: 61AN XY: 682586
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GnomAD4 genome AF: 0.000184 AC: 28AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74362
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Joubert syndrome 23;C4225286:Short-rib thoracic dysplasia 14 with polydactyly Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 01, 2024 | This sequence change affects the initiator methionine of the KIAA0586 mRNA. The next in-frame methionine is located at codon 13. This variant is present in population databases (rs753810786, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with KIAA0586-related conditions. ClinVar contains an entry for this variant (Variation ID: 1375585). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Vest4
MutPred
Loss of disorder (P = 0.0444);
MVP
ClinPred
T
GERP RS
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at