20-21161882-C-G

Variant names:

• chr20-21161882-C-G
• rs4815025
• NM_018474.6:c.417C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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 the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H139R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.58 (27090 hom., cov: 30)
  • Exomes 𝑓: 0.66 (325246 hom.)
• Consequence: KIZ NM_018474.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0620

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-AS1 (HGNC:51231): (KIZ antisense RNA 1)

ENSG00000228604 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
KIZ	NM_018474.6	c.417C>G	p.His139Gln	missense_variant	Exon 5 of 13	ENST00000619189.5	NP_060944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIZ	ENST00000619189.5	c.417C>G	p.His139Gln	missense_variant	Exon 5 of 13	1	NM_018474.6	ENSP00000479542.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87862 AN: 151470 Hom.: 27079 Cov.: 30

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

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.: 33 AF XY: 0.671 AC XY: 486456 AN XY: 724726

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.: 30 AF XY: 0.585 AC XY: 43338 AN XY: 74054

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

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Retinal dystrophy Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.26
DANN	Benign	0.66
DEOGEN2	Benign	0.0079	T;.;.;T;.;.
FATHMM_MKL	Benign	0.00034	N
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	T
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

Other links and lift over

dbSNP: rs4815025; hg19: chr20-21142523; COSMIC: COSV55685121; COSMIC: COSV55685121;