rs1414225320

Variant names:

• chr20-21126050-C-G
• rs1414225320
• ENST00000620891.4:c.-212C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-21126050-C-G
• chr20-21126050-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001276389.2(KIZ):​c.14C>G​(p.Ser5Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,411,576 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: KIZ NM_001276389.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.398
• Publications: 1 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 Gene-Disease associations (from GenCC):

• KIZ-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 69

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15330902).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276389.2. 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_001276389.2		c.14C>G	p.Ser5Cys	missense	Exon 1 of 11	NP_001263318.1	A0A087X251
	KIZ	NM_018474.6	MANE Select	c.-66C>G		upstream_gene	N/A	NP_060944.3
	KIZ	NM_001352434.2		c.-66C>G		upstream_gene	N/A	NP_001339363.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIZ	ENST00000620891.4	TSL:1	c.-212C>G		5_prime_UTR	Exon 1 of 12	ENSP00000478019.1	Q2M2Z5-2
	KIZ	ENST00000619574.4	TSL:2	c.14C>G	p.Ser5Cys	missense	Exon 1 of 11	ENSP00000484706.1	A0A087X251
	KIZ	ENST00000611685.4	TSL:2	c.11C>G	p.Ser4Cys	missense	Exon 1 of 11	ENSP00000483644.2	A0A087X251

Frequencies

GnomAD3 genomes AF: 0.00000718 AC: 1 AN: 139246 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000214

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000236 AC: 3 AN: 1272330 Hom.: 0 Cov.: 29 AF XY: 0.00000161 AC XY: 1 AN XY: 621892

African (AFR) AF: 0.00 AC: 0 AN: 26052

American (AMR) AF: 0.00 AC: 0 AN: 21972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20334

East Asian (EAS) AF: 0.000108 AC: 3 AN: 27880

South Asian (SAS) AF: 0.00 AC: 0 AN: 65270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4602

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1021260

Other (OTH) AF: 0.00 AC: 0 AN: 52412

GnomAD4 genome AF: 0.00000718 AC: 1 AN: 139246 Hom.: 0 Cov.: 32 AF XY: 0.0000149 AC XY: 1 AN XY: 67314

African (AFR) AF: 0.00 AC: 0 AN: 39968

American (AMR) AF: 0.00 AC: 0 AN: 13766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3196

East Asian (EAS) AF: 0.000214 AC: 1 AN: 4668

South Asian (SAS) AF: 0.00 AC: 0 AN: 3866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62156

Other (OTH) AF: 0.00 AC: 0 AN: 1844

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	12
DANN	Benign	0.78
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.15	T
PhyloP100		0.40
Sift4G	Benign	0.064	T
Vest4		0.31
MVP		0.28
GERP RS		3.1
PromoterAI		0.055	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1414225320; hg19: chr20-21106691;