20-21126167-GAG-AAA

Variant names:

• chr20-21126167-GAG-AAA
• NM_018474.6:c.52_54delGAGinsAAA
• KIZ p.Glu18Lys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018474.6(KIZ):​c.52_54delGAGinsAAA​(p.Glu18Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIZ NM_018474.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• 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: G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018474.6. 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_018474.6	MANE Select	c.52_54delGAGinsAAA	p.Glu18Lys	missense	N/A	NP_060944.3
	KIZ	NM_001352434.2		c.52_54delGAGinsAAA	p.Glu18Lys	missense	N/A	NP_001339363.1
	KIZ	NM_001276389.2		c.131_133delGAGinsAAA	p.ArgGlu44GlnLys	missense	N/A	NP_001263318.1	A0A087X251

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIZ	ENST00000619189.5	TSL:1 MANE Select	c.52_54delGAGinsAAA	p.Glu18Lys	missense	N/A	ENSP00000479542.1	Q2M2Z5-1
	KIZ	ENST00000620891.4	TSL:1	c.-95_-93delGAGinsAAA		5_prime_UTR	Exon 1 of 12	ENSP00000478019.1	Q2M2Z5-2
	KIZ	ENST00000962859.1		c.52_54delGAGinsAAA	p.Glu18Lys	missense	N/A	ENSP00000632918.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-21106808;