NM_018474.6:c.52G>A

Variant names:

• chr20-21126167-G-A
• rs587777376
• NM_018474.6:c.52G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_018474.6(KIZ):​c.52G>A​(p.Glu18Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 1,356,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• 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: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30978382).

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.52G>A	p.Glu18Lys	missense	Exon 1 of 13	NP_060944.3
	KIZ	NM_001352434.2		c.52G>A	p.Glu18Lys	missense	Exon 1 of 13	NP_001339363.1
	KIZ	NM_001276389.2		c.131G>A	p.Arg44Gln	missense	Exon 1 of 11	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.52G>A	p.Glu18Lys	missense	Exon 1 of 13	ENSP00000479542.1	Q2M2Z5-1
	KIZ	ENST00000620891.4	TSL:1	c.-95G>A		5_prime_UTR	Exon 1 of 12	ENSP00000478019.1	Q2M2Z5-2
	KIZ	ENST00000962859.1		c.52G>A	p.Glu18Lys	missense	Exon 1 of 13	ENSP00000632918.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000133 AC: 18 AN: 1356692 Hom.: 0 Cov.: 32 AF XY: 0.0000150 AC XY: 10 AN XY: 668280

African (AFR) AF: 0.00 AC: 0 AN: 27784

American (AMR) AF: 0.00 AC: 0 AN: 31660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23610

East Asian (EAS) AF: 0.00 AC: 0 AN: 30412

South Asian (SAS) AF: 0.00 AC: 0 AN: 75504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46790

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5486

European-Non Finnish (NFE) AF: 0.0000160 AC: 17 AN: 1059364

Other (OTH) AF: 0.0000178 AC: 1 AN: 56082

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	22
DANN	Benign	0.89
DEOGEN2	Benign	0.030	T
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.31	T
PhyloP100		2.0
PrimateAI	Uncertain	0.71	T
Sift4G	Benign	0.29	T
Polyphen		0.97	D
Vest4		0.32
MVP		0.23
GERP RS		4.1
PromoterAI		-0.059	Neutral
Varity_R		0.15
gMVP		0.18

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: rs587777376; hg19: chr20-21106808;