rs4815025

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-21161882-C-A
• chr20-21161882-C-G
• chr20-21161882-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018474.6(KIZ):​c.417C>A​(p.His139Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIZ NM_018474.6 missense
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.020322412).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459004 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725872

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.21
DANN	Benign	0.73
DEOGEN2	Benign	0.0079	T;.;.;T;.;.
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.0084	T;T;T;T;T;T
MetaRNN	Benign	0.020	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
MVP		0.14
GERP RS		0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.054
gMVP		0.11

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

Other links and lift over

dbSNP: rs4815025; hg19: chr20-21142523;