rs193920844

Variant names:

• chr14-75101740-G-GT
• rs193920844
• NM_033116.6:c.1756dupA

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_033116.6(NEK9):​c.1756dupA​(p.Thr586AsnfsTer13) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NEK9 NM_033116.6 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.56
• Publications: 0 publications found

Genes affected

NEK9 (HGNC:18591): (NIMA related kinase 9) This gene encodes a member of the NimA (never in mitosis A) family of serine/threonine protein kinases. The encoded protein is activated in mitosis and, in turn, activates other family members during mitosis. This protein also mediates cellular processes that are essential for interphase progression. [provided by RefSeq, Jul 2016]

ZC2HC1C (HGNC:20354): (zinc finger C2HC-type containing 1C) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZC2HC1C Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033116.6. 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
	NEK9	NM_033116.6	MANE Select	c.1756dupA	p.Thr586AsnfsTer13	frameshift	Exon 15 of 22	NP_149107.4
	NEK9	NM_001329237.2		c.1792dupA	p.Thr598AsnfsTer13	frameshift	Exon 15 of 22	NP_001316166.1	A0A7I2V5R1
	NEK9	NM_001329238.2		c.1402dupA	p.Thr468AsnfsTer13	frameshift	Exon 15 of 22	NP_001316167.1	A0A7I2V454

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEK9	ENST00000238616.10	TSL:1 MANE Select	c.1756dupA	p.Thr586AsnfsTer13	frameshift	Exon 15 of 22	ENSP00000238616.5	Q8TD19
	NEK9	ENST00000678037.1		c.1792dupA	p.Thr598AsnfsTer13	frameshift	Exon 15 of 22	ENSP00000504620.1	A0A7I2V5R1
	NEK9	ENST00000909801.1		c.1762dupA	p.Thr588AsnfsTer13	frameshift	Exon 15 of 22	ENSP00000579860.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.6

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

Other links and lift over

dbSNP: rs193920844; hg19: chr14-75568443; COSMIC: COSV53133910; COSMIC: COSV53133910;