rs61735931
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 8P and 12B. PVS1BP6_Very_StrongBS2
The NM_001244193.2(KIAA0586):āc.2T>Cā(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00673 in 1,567,602 control chromosomes in the GnomAD database, including 54 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 0.0052 ( 3 hom., cov: 33)
Exomes š: 0.0069 ( 51 hom. )
Consequence
KIAA0586
NM_001244193.2 start_lost
NM_001244193.2 start_lost
Scores
18
Clinical Significance
Conservation
PhyloP100: 0.497
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 Likely_benign. Variant got -4 ACMG points.
PVS1
Start lost variant, no new inframe start found.
BP6
Variant 14-58442717-T-C is Benign according to our data. Variant chr14-58442717-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 377258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KIAA0586 | NM_001329943.3 | c.422T>C | p.Met141Thr | missense_variant | 5/31 | ENST00000652326.2 | NP_001316872.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KIAA0586 | ENST00000652326.2 | c.422T>C | p.Met141Thr | missense_variant | 5/31 | NM_001329943.3 | ENSP00000498929.1 |
Frequencies
GnomAD3 genomes AF: 0.00519 AC: 790AN: 152196Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.00509 AC: 939AN: 184644Hom.: 6 AF XY: 0.00490 AC XY: 482AN XY: 98274
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GnomAD4 exome AF: 0.00690 AC: 9766AN: 1415288Hom.: 51 Cov.: 29 AF XY: 0.00682 AC XY: 4774AN XY: 699890
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GnomAD4 genome AF: 0.00519 AC: 790AN: 152314Hom.: 3 Cov.: 33 AF XY: 0.00458 AC XY: 341AN XY: 74472
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2024 | KIAA0586: BP4, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jan 24, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 21, 2019 | - - |
Joubert syndrome 23;C4225286:Short-rib thoracic dysplasia 14 with polydactyly Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;.;T;T;.;T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;.;T;T;T
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;L;.;.;.;.
PrimateAI
Benign
T
PROVEAN
Benign
N;.;.;.;N;N;N;N
REVEL
Benign
Sift
Benign
T;.;.;.;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T
Polyphen
0.0030
.;.;.;B;.;.;.;.
Vest4
MVP
MPC
ClinPred
T
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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