NM_001329943.3:c.831C>T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM2PP5_ModerateBP4BP7
The NM_001329943.3(KIAA0586):c.831C>T(p.Leu277Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000968 in 1,445,542 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 Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L277L) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000097 ( 0 hom. )
Consequence
KIAA0586
NM_001329943.3 synonymous
NM_001329943.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.383
Publications
1 publications found
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]
KIAA0586 Gene-Disease associations (from GenCC):
- Joubert syndrome 23Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- short-rib thoracic dysplasia 14 with polydactylyInheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
- Joubert syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Joubert syndrome with Jeune asphyxiating thoracic dystrophyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-58448363-C-T is Pathogenic according to our data. Variant chr14-58448363-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 475455.Status of the report is criteria_provided_single_submitter, 1 stars.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65). . Strength limited to SUPPORTING due to the PP5.
BP7
Synonymous conserved (PhyloP=0.383 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001329943.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| KIAA0586 | NM_001329943.3 | MANE Select | c.831C>T | p.Leu277Leu | synonymous | Exon 7 of 31 | NP_001316872.1 | A0A494C171 | |
| KIAA0586 | NM_001244189.2 | c.990C>T | p.Leu330Leu | synonymous | Exon 9 of 34 | NP_001231118.1 | Q9BVV6-3 | ||
| KIAA0586 | NM_001329944.2 | c.831C>T | p.Leu277Leu | synonymous | Exon 7 of 32 | NP_001316873.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| KIAA0586 | ENST00000652326.2 | MANE Select | c.831C>T | p.Leu277Leu | synonymous | Exon 7 of 31 | ENSP00000498929.1 | A0A494C171 | |
| KIAA0586 | ENST00000619416.4 | TSL:1 | c.786C>T | p.Leu262Leu | synonymous | Exon 8 of 32 | ENSP00000478083.1 | Q9BVV6-1 | |
| KIAA0586 | ENST00000423743.7 | TSL:1 | c.699C>T | p.Leu233Leu | synonymous | Exon 8 of 32 | ENSP00000399427.3 | Q9BVV6-4 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.0000285 AC: 7AN: 245872 AF XY: 0.0000450 show subpopulations
GnomAD2 exomes
AF:
AC:
7
AN:
245872
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000968 AC: 14AN: 1445542Hom.: 0 Cov.: 27 AF XY: 0.0000125 AC XY: 9AN XY: 719836 show subpopulations
GnomAD4 exome
AF:
AC:
14
AN:
1445542
Hom.:
Cov.:
27
AF XY:
AC XY:
9
AN XY:
719836
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33034
American (AMR)
AF:
AC:
0
AN:
43722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25944
East Asian (EAS)
AF:
AC:
0
AN:
39518
South Asian (SAS)
AF:
AC:
0
AN:
84976
European-Finnish (FIN)
AF:
AC:
0
AN:
53286
Middle Eastern (MID)
AF:
AC:
0
AN:
5726
European-Non Finnish (NFE)
AF:
AC:
14
AN:
1099548
Other (OTH)
AF:
AC:
0
AN:
59788
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.514
Heterozygous variant carriers
0
1
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6
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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<30
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Joubert syndrome 23;C4225286:Short-rib thoracic dysplasia 14 with polydactyly (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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