chr20-21126073-C-CT

Variant names:

• chr20-21126073-C-CT
• rs1555868165
• ENST00000620891.4:c.-189_-188insT

Variant summary

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

The NM_001276389.2(KIZ):​c.37_38insT​(p.Arg13LeufsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIZ NM_001276389.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62
• Publications: 0 publications found

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

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIZ	NM_001276389.2		c.37_38insT	p.Arg13LeufsTer8	frameshift	Exon 1 of 11	NP_001263318.1	A0A087X251
	KIZ	NM_018474.6	MANE Select	c.-43_-42insT		upstream_gene	N/A	NP_060944.3
	KIZ	NM_001352434.2		c.-43_-42insT		upstream_gene	N/A	NP_001339363.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIZ	ENST00000620891.4	TSL:1	c.-189_-188insT		5_prime_UTR	Exon 1 of 12	ENSP00000478019.1	Q2M2Z5-2
	KIZ	ENST00000619574.4	TSL:2	c.37_38insT	p.Arg13LeufsTer8	frameshift	Exon 1 of 11	ENSP00000484706.1	A0A087X251
	KIZ	ENST00000611685.4	TSL:2	c.34_35insT	p.Arg12GlyfsTer63	frameshift	Exon 1 of 11	ENSP00000483644.2	A0A087X251

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152044 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1309624 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 642976

African (AFR) AF: 0.00 AC: 0 AN: 26516

American (AMR) AF: 0.00 AC: 0 AN: 25220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22332

East Asian (EAS) AF: 0.00 AC: 0 AN: 28438

South Asian (SAS) AF: 0.00 AC: 0 AN: 71008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5108

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1039794

Other (OTH) AF: 0.00 AC: 0 AN: 54104

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152044 Hom.: 0 Cov.: 0 AF XY: 0.0000135 AC XY: 1 AN XY: 74252

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

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

Other links and lift over

dbSNP: rs1555868165; hg19: chr20-21106714;