Genetic Variant KIZ:c.-212C>T (chr20-21126050-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001276389.2(KIZ):c.14C>T(p.Ser5Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000786 in 1,272,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S5C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

KIZ
NM_001276389.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.398

Publications

1 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: G2P, Labcorp Genetics (formerly Invitae)
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KIZ links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16796696).

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.14C>T	p.Ser5Phe	missense	Exon 1 of 11	NP_001263318.1	A0A087X251
KIZ	NM_018474.6	MANE Select	c.-66C>T		upstream_gene	N/A	NP_060944.3
KIZ	NM_001352434.2		c.-66C>T		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.-212C>T		5_prime_UTR	Exon 1 of 12	ENSP00000478019.1	Q2M2Z5-2
KIZ	ENST00000619574.4	TSL:2	c.14C>T	p.Ser5Phe	missense	Exon 1 of 11	ENSP00000484706.1	A0A087X251
KIZ	ENST00000611685.4	TSL:2	c.11C>T	p.Ser4Phe	missense	Exon 1 of 11	ENSP00000483644.2	A0A087X251

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.86e-7

AC:

AN:

1272330

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

621892

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26052

American (AMR)

AF:

0.00

AC:

AN:

21972

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20334

East Asian (EAS)

AF:

0.00

AC:

AN:

27880

South Asian (SAS)

AF:

0.00

AC:

AN:

65270

European-Finnish (FIN)

AF:

0.0000307

AC:

AN:

32548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4602

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1021260

Other (OTH)

AF:

0.00

AC:

AN:

52412

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.42

MetaRNN

Benign

0.17

PhyloP100

0.40

Sift4G

Benign

0.069

Vest4

0.31

MVP

0.29

GERP RS

3.1

PromoterAI

-0.33

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over