chr20-21161882-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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 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
• Publications: 37 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018474.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIZ	NM_018474.6	MANE Select	c.417C>G	p.His139Gln	missense	Exon 5 of 13	NP_060944.3
	KIZ	NM_001352434.2		c.417C>G	p.His139Gln	missense	Exon 5 of 13	NP_001339363.1
	KIZ	NM_001276389.2		c.270C>G	p.His90Gln	missense	Exon 3 of 11	NP_001263318.1	A0A087X251

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIZ	ENST00000619189.5	TSL:1 MANE Select	c.417C>G	p.His139Gln	missense	Exon 5 of 13	ENSP00000479542.1	Q2M2Z5-1
	KIZ	ENST00000620891.4	TSL:1	c.108C>G	p.His36Gln	missense	Exon 4 of 12	ENSP00000478019.1	Q2M2Z5-2
	KIZ-AS1	ENST00000616177.4	TSL:1	n.5143+914G>C		intron	N/A

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

GnomAD2 exomes AF: 0.646 AC: 160031 AN: 247878 AF XY: 0.664

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 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

African (AFR) AF: 0.350 AC: 11676 AN: 33360

American (AMR) AF: 0.533 AC: 23795 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 18665 AN: 26030

East Asian (EAS) AF: 0.527 AC: 20917 AN: 39662

South Asian (SAS) AF: 0.779 AC: 67083 AN: 86108

European-Finnish (FIN) AF: 0.694 AC: 37051 AN: 53362

Middle Eastern (MID) AF: 0.744 AC: 4276 AN: 5746

European-Non Finnish (NFE) AF: 0.672 AC: 744443 AN: 1107270

Other (OTH) AF: 0.659 AC: 39668 AN: 60182

GnomAD4 genome AF: 0.580 AC: 87914 AN: 151582 Hom.: 27090 Cov.: 30 AF XY: 0.585 AC XY: 43338 AN XY: 74054

African (AFR) AF: 0.357 AC: 14727 AN: 41244

American (AMR) AF: 0.578 AC: 8810 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2469 AN: 3472

East Asian (EAS) AF: 0.552 AC: 2840 AN: 5146

South Asian (SAS) AF: 0.778 AC: 3741 AN: 4810

European-Finnish (FIN) AF: 0.710 AC: 7411 AN: 10438

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45813 AN: 67928

Other (OTH) AF: 0.648 AC: 1367 AN: 2108

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

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
FATHMM_MKL	Benign	0.00034	N
LIST_S2	Benign	0.0084	T
MetaRNN	Benign	7.2e-7	T
MutationAssessor	Benign	-1.8	N
PhyloP100		-0.062
PrimateAI	Benign	0.27	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.032
GERP RS		0.92
PromoterAI		0.0098	Neutral
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

Other links and lift over

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