Variant chr20-21161974-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018474.6(KIZ):c.509T>G(p.Met170Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,613,976 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 22 hom., cov: 32)

Exomes 𝑓: 0.00087 ( 18 hom. )

Consequence

KIZ
NM_018474.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.687

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 links:

KIZ-AS1 (HGNC:):

KIZ-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004019022).

BP6

Variant 20-21161974-T-G is Benign according to our data. Variant chr20-21161974-T-G is described in ClinVar as [Benign]. Clinvar id is 786967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00842 (1282/152328) while in subpopulation AFR AF= 0.0293 (1219/41564). AF 95% confidence interval is 0.028. There are 22 homozygotes in gnomad4. There are 606 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIZ	NM_018474.6 linkuse as main transcript	c.509T>G	p.Met170Arg	missense_variant	5/13	ENST00000619189.5	NP_060944.3	Q2M2Z5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIZ	ENST00000619189.5 linkuse as main transcript	c.509T>G	p.Met170Arg	missense_variant	5/13	1	NM_018474.6	ENSP00000479542.1		Q2M2Z5-1

Frequencies

GnomAD3 genomes

AF:

0.00842

AC:

1281

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0294

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00211

AC:

525

AN:

249012

Hom.:

AF XY:

0.00147

AC XY:

198

AN XY:

135078

show subpopulations

Gnomad AFR exome

AF:

0.0303

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000620

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000866

AC:

1266

AN:

1461648

Hom.:

Cov.:

AF XY:

0.000734

AC XY:

534

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.0307

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000459

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.00842

AC:

1282

AN:

152328

Hom.:

Cov.:

AF XY:

0.00813

AC XY:

606

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0293

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.00936

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0279

AC:

107

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00270

AC:

326

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jan 05, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.089

T;.;.;T;.;.

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.79

T;T;T;T;T;T

MetaRNN

Benign

0.0040

T;T;T;T;T;T

MutationAssessor

Benign

0.90

.;.;.;L;.;.

PrimateAI

Benign

0.25

Sift4G

Benign

0.49

T;T;T;T;T;T

Polyphen

0.63, 0.48, 0.83

.;P;P;P;.;.

Vest4

0.24

MVP

0.27

GERP RS

3.0

Varity_R

0.75

gMVP

0.30

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over