Variant 20-21161882-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018474.6(KIZ):c.417C>G(p.His139Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,607,958 control chromosomes in the GnomAD database, including 352,336 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. H139H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.58 ( 27090 hom., cov: 30)

Exomes 𝑓: 0.66 ( 325246 hom. )

Consequence

KIZ
NM_018474.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0620

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=7.2050227E-7).

BP6

Variant 20-21161882-C-G is Benign according to our data. Variant chr20-21161882-C-G is described in ClinVar as [Benign]. Clinvar id is 1165622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIZ	NM_018474.6 linkuse as main transcript	c.417C>G	p.His139Gln	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.417C>G	p.His139Gln	missense_variant	5/13	1	NM_018474.6	ENSP00000479542.1		Q2M2Z5-1

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

87862

AN:

151470

Hom.:

27079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.357

Gnomad AMI

AF:

0.573

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.711

Gnomad EAS

AF:

0.552

Gnomad SAS

AF:

0.776

Gnomad FIN

AF:

0.710

Gnomad MID

AF:

0.737

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.649

GnomAD3 exomes

AF:

0.646

AC:

160031

AN:

247878

Hom.:

53158

AF XY:

0.664

AC XY:

89208

AN XY:

134412

show subpopulations

Gnomad AFR exome

AF:

0.347

Gnomad AMR exome

AF:

0.524

Gnomad ASJ exome

AF:

0.721

Gnomad EAS exome

AF:

0.565

Gnomad SAS exome

AF:

0.780

Gnomad FIN exome

AF:

0.698

Gnomad NFE exome

AF:

0.682

Gnomad OTH exome

AF:

0.674

GnomAD4 exome

AF:

0.664

AC:

967574

AN:

1456376

Hom.:

325246

Cov.:

AF XY:

0.671

AC XY:

486456

AN XY:

724726

show subpopulations

Gnomad4 AFR exome

AF:

0.350

Gnomad4 AMR exome

AF:

0.533

Gnomad4 ASJ exome

AF:

0.717

Gnomad4 EAS exome

AF:

0.527

Gnomad4 SAS exome

AF:

0.779

Gnomad4 FIN exome

AF:

0.694

Gnomad4 NFE exome

AF:

0.672

Gnomad4 OTH exome

AF:

0.659

GnomAD4 genome

AF:

0.580

AC:

87914

AN:

151582

Hom.:

27090

Cov.:

AF XY:

0.585

AC XY:

43338

AN XY:

74054

show subpopulations

Gnomad4 AFR

AF:

0.357

Gnomad4 AMR

AF:

0.578

Gnomad4 ASJ

AF:

0.711

Gnomad4 EAS

AF:

0.552

Gnomad4 SAS

AF:

0.778

Gnomad4 FIN

AF:

0.710

Gnomad4 NFE

AF:

0.674

Gnomad4 OTH

AF:

0.648

Alfa

AF:

0.650

Hom.:

18161

Bravo

AF:

0.555

TwinsUK

AF:

0.686

AC:

2545

ALSPAC

AF:

0.658

AC:

2536

ESP6500AA

AF:

0.379

AC:

1445

ESP6500EA

AF:

0.680

AC:

5594

ExAC

AF:

0.648

AC:

78244

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.26

DANN

Benign

0.66

DEOGEN2

Benign

0.0079

T;.;.;T;.;.

FATHMM_MKL

Benign

0.00034

LIST_S2

Benign

0.0084

T;T;T;T;T;T

MetaRNN

Benign

7.2e-7

T;T;T;T;T;T

MutationAssessor

Benign

-1.8

.;.;.;N;.;.

PrimateAI

Benign

0.27

Sift4G

Benign

0.47

T;T;T;T;T;T

Polyphen

0.0

.;B;B;B;.;.

Vest4

0.032

GERP RS

0.92

Varity_R

0.054

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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