Genetic Variant KIZ:c.-212C>G (chr20-21126050-C-G) – 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>G(p.Ser5Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,411,576 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

KIZ
NM_001276389.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

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=0.15330902).

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>G	p.Ser5Cys	missense	Exon 1 of 11	NP_001263318.1	A0A087X251
KIZ	NM_018474.6	MANE Select	c.-66C>G		upstream_gene	N/A	NP_060944.3
KIZ	NM_001352434.2		c.-66C>G		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>G		5_prime_UTR	Exon 1 of 12	ENSP00000478019.1	Q2M2Z5-2
KIZ	ENST00000619574.4	TSL:2	c.14C>G	p.Ser5Cys	missense	Exon 1 of 11	ENSP00000484706.1	A0A087X251
KIZ	ENST00000611685.4	TSL:2	c.11C>G	p.Ser4Cys	missense	Exon 1 of 11	ENSP00000483644.2	A0A087X251

Frequencies

GnomAD3 genomes

AF:

0.00000718

AC:

AN:

139246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000214

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000236

AC:

AN:

1272330

Hom.:

Cov.:

AF XY:

0.00000161

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:

0.000108

AC:

AN:

27880

South Asian (SAS)

AF:

0.00

AC:

AN:

65270

European-Finnish (FIN)

AF:

0.00

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: 0.558

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:

0.00000718

AC:

AN:

139246

Hom.:

Cov.:

AF XY:

0.0000149

AC XY:

AN XY:

67314

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39968

American (AMR)

AF:

0.00

AC:

AN:

13766

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3196

East Asian (EAS)

AF:

0.000214

AC:

AN:

4668

South Asian (SAS)

AF:

0.00

AC:

AN:

3866

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

62156

Other (OTH)

AF:

0.00

AC:

AN:

1844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.37

MetaRNN

Benign

0.15

PhyloP100

0.40

Sift4G

Benign

0.064

Vest4

0.31

MVP

0.28

GERP RS

3.1

PromoterAI

0.055

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over