rs587777376
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_018474.6(KIZ):c.52G>T(p.Glu18Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000464 in 1,508,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000044 ( 0 hom. )
Consequence
KIZ
NM_018474.6 stop_gained
NM_018474.6 stop_gained
Scores
1
1
2
Clinical Significance
Conservation
PhyloP100: 2.00
Genes affected
KIZ (HGNC:15865): (kizuna centrosomal protein) The protein encoded by this gene localizes to centrosomes, strengthening and stabilizing the pericentriolar region prior to spindle formation. The encoded protein usually remains with the mother centrosome after centrosomal duplication. Sevral transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 23 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
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Variant 20-21126167-G-T is Pathogenic according to our data. Variant chr20-21126167-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 128242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-21126167-G-T is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIZ | NM_018474.6 | c.52G>T | p.Glu18Ter | stop_gained | 1/13 | ENST00000619189.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIZ | ENST00000619189.5 | c.52G>T | p.Glu18Ter | stop_gained | 1/13 | 1 | NM_018474.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000442 AC: 6AN: 1356692Hom.: 0 Cov.: 32 AF XY: 0.00000449 AC XY: 3AN XY: 668280
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74370
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Retinitis pigmentosa 69 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 03, 2014 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 03, 2023 | This sequence change creates a premature translational stop signal (p.Glu18*) in the KIZ gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KIZ are known to be pathogenic (PMID: 24680887, 29057815). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with KIZ-related conditions (PMID: 24680887). ClinVar contains an entry for this variant (Variation ID: 128242). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Benign
FATHMM_MKL
Uncertain
D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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