NM_018474.6:c.417C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_018474.6(KIZ):​c.417C>T​(p.His139His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,610,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: KIZ NM_018474.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 20-21161882-C-T is Benign according to our data. Variant chr20-21161882-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1112418.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.062 with no splicing effect.

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>T	p.His139His	synonymous	Exon 5 of 13	NP_060944.3
	KIZ	NM_001352434.2		c.417C>T	p.His139His	synonymous	Exon 5 of 13	NP_001339363.1
	KIZ	NM_001276389.2		c.270C>T	p.His90His	synonymous	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>T	p.His139His	synonymous	Exon 5 of 13	ENSP00000479542.1	Q2M2Z5-1
	KIZ	ENST00000620891.4	TSL:1	c.108C>T	p.His36His	synonymous	Exon 4 of 12	ENSP00000478019.1	Q2M2Z5-2
	KIZ-AS1	ENST00000616177.4	TSL:1	n.5143+914G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000858 AC: 13 AN: 151554 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000486

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000686 AC: 17 AN: 247878 AF XY: 0.0000595

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000152

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000197 AC: 288 AN: 1459006 Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 127 AN XY: 725874

African (AFR) AF: 0.0000299 AC: 1 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.000246 AC: 273 AN: 1109642

Other (OTH) AF: 0.000232 AC: 14 AN: 60276

GnomAD4 genome AF: 0.0000858 AC: 13 AN: 151554 Hom.: 0 Cov.: 30 AF XY: 0.0000541 AC XY: 4 AN XY: 73982

African (AFR) AF: 0.0000486 AC: 2 AN: 41148

American (AMR) AF: 0.00 AC: 0 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67956

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000119 Hom.: 18161

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	KIZ-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.3
DANN	Benign	0.87
PhyloP100		-0.062
PromoterAI		-0.0084	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;