Genetic Variant KIZ:c.-189_-188insA (chr20-21126073-C-CA) – ACMG Classification: Likely_pathogenic (8 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1

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

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.62

Publications

0 publications found

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]

KIZ Gene-Disease associations (from GenCC):

KIZ-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa 69
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KIZ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 8 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 31 pathogenic variants in the truncated region.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276389.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIZ	NM_001276389.2		c.37_38insA	p.Arg13GlnfsTer8	frameshift	Exon 1 of 11	NP_001263318.1	A0A087X251
KIZ	NM_018474.6	MANE Select	c.-43_-42insA		upstream_gene	N/A	NP_060944.3
KIZ	NM_001352434.2		c.-43_-42insA		upstream_gene	N/A	NP_001339363.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIZ	ENST00000620891.4	TSL:1	c.-189_-188insA		5_prime_UTR	Exon 1 of 12	ENSP00000478019.1	Q2M2Z5-2
KIZ	ENST00000619574.4	TSL:2	c.37_38insA	p.Arg13GlnfsTer8	frameshift	Exon 1 of 11	ENSP00000484706.1	A0A087X251
KIZ	ENST00000611685.4	TSL:2	c.34_35insA	p.Arg12GlyfsTer63	frameshift	Exon 1 of 11	ENSP00000483644.2	A0A087X251

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000135

AC:

AN:

74190

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000363

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000367

AC:

AN:

1309622

Hom.:

Cov.:

AF XY:

0.0000451

AC XY:

AN XY:

642976

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26516

American (AMR)

AF:

0.00

AC:

AN:

25220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22332

East Asian (EAS)

AF:

0.00

AC:

AN:

28438

South Asian (SAS)

AF:

0.00

AC:

AN:

71006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5108

European-Non Finnish (NFE)

AF:

0.0000414

AC:

AN:

1039794

Other (OTH)

AF:

0.0000924

AC:

AN:

54104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152044

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67958

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000148

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-2.6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over