20-21126142-G-A

Position:

• chr20-21126142-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001276389.2(KIZ):​c.106G>A​(p.Ala36Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000294 in 1,362,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: KIZ NM_001276389.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.773

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 (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=0.07613319).
• BP6: Variant 20-21126142-G-A is Benign according to our data. Variant chr20-21126142-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1655533.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIZ	NM_018474.6	c.27G>A	p.Val9Val	synonymous_variant	1/13	ENST00000619189.5	NP_060944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIZ	ENST00000619189.5	c.27G>A	p.Val9Val	synonymous_variant	1/13	1	NM_018474.6	ENSP00000479542.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000173 AC: 2 AN: 115906 Hom.: 0 AF XY: 0.0000315 AC XY: 2 AN XY: 63546

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000486

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000231

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000294 AC: 4 AN: 1362228 Hom.: 0 Cov.: 32 AF XY: 0.00000298 AC XY: 2 AN XY: 671428

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000308

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: 0.00000282

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.6
DANN	Benign	0.66
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.076	T
Sift4G	Uncertain	0.045	D
Vest4		0.13
MVP		0.18
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs747021291; hg19: chr20-21106783;