20-21126128-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018474.6(KIZ):​c.13C>T​(p.Leu5Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000022 in 1,362,984 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000022 ( 1 hom. )

Consequence

KIZ
NM_018474.6 missense

Scores

10

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.198
Variant links:
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_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.057834953).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIZNM_018474.6 linkc.13C>T p.Leu5Phe missense_variant Exon 1 of 13 ENST00000619189.5 NP_060944.3 Q2M2Z5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIZENST00000619189.5 linkc.13C>T p.Leu5Phe missense_variant Exon 1 of 13 1 NM_018474.6 ENSP00000479542.1 Q2M2Z5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000220
AC:
3
AN:
1362984
Hom.:
1
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
672044
show subpopulations
Gnomad4 AFR exome
AF:
0.0000358
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000649
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.13C>T (p.L5F) alteration is located in exon 1 (coding exon 1) of the KIZ gene. This alteration results from a C to T substitution at nucleotide position 13, causing the leucine (L) at amino acid position 5 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Uncertain:1
Dec 02, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 5 of the KIZ protein (p.Leu5Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KIZ-related conditions. ClinVar contains an entry for this variant (Variation ID: 1359249). 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
1.2
DANN
Benign
0.77
DEOGEN2
Benign
0.011
T
FATHMM_MKL
Benign
0.0088
N
LIST_S2
Benign
0.37
T
MetaRNN
Benign
0.058
T
PrimateAI
Benign
0.47
T
Sift4G
Benign
0.33
T
Polyphen
0.0
B
Vest4
0.072
MVP
0.21
GERP RS
0.41
Varity_R
0.040
gMVP
0.077

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1351290157; hg19: chr20-21106769; COSMIC: COSV55688085; API