20-21126073-C-CA
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_001276389.2(KIZ):c.37_38insA(p.Arg13GlnfsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000376 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000037 ( 0 hom. )
Consequence
KIZ
NM_001276389.2 frameshift
NM_001276389.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -2.62
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 Likely_pathogenic. Variant got 6 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. Fraction of 0.98 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152044Hom.: 0 Cov.: 0
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GnomAD3 exomes AF: 0.0000135 AC: 1AN: 74190Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 42208
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GnomAD4 exome AF: 0.0000367 AC: 48AN: 1309622Hom.: 0 Cov.: 34 AF XY: 0.0000451 AC XY: 29AN XY: 642976
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152044Hom.: 0 Cov.: 0 AF XY: 0.0000673 AC XY: 5AN XY: 74252
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Aug 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at