Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP5

The NM_033116.6(NEK9):c.1718T>C(p.Ile573Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I573V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

NEK9
NM_033116.6 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.23

Publications

1 publications found

Variant links:

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]

NEK9 links:

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

ZC2HC1C links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 14-75103855-A-G is Pathogenic according to our data. Variant chr14-75103855-A-G is described in ClinVar as Pathogenic. ClinVar VariationId is 242988.Status of the report is no_assertion_criteria_provided, 0 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NEK9	NM_033116.6	MANE Select	c.1718T>C	p.Ile573Thr	missense	Exon 14 of 22	NP_149107.4
NEK9	NM_001329237.2		c.1754T>C	p.Ile585Thr	missense	Exon 14 of 22	NP_001316166.1
NEK9	NM_001329238.2		c.1364T>C	p.Ile455Thr	missense	Exon 14 of 22	NP_001316167.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NEK9	ENST00000238616.10	TSL:1 MANE Select	c.1718T>C	p.Ile573Thr	missense	Exon 14 of 22	ENSP00000238616.5
NEK9	ENST00000678037.1		c.1754T>C	p.Ile585Thr	missense	Exon 14 of 22	ENSP00000504620.1
NEK9	ENST00000678531.1		c.1364T>C	p.Ile455Thr	missense	Exon 14 of 22	ENSP00000503827.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nevus comedonicus syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.071

Eigen

Uncertain

0.61

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-0.46

MutationAssessor

Benign

1.9

PhyloP100

9.2

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.33

Sift

Benign

0.14

Sift4G

Uncertain

0.015

Polyphen

0.98

Vest4

0.63

MutPred

0.36

Loss of stability (P = 0.0141)

MVP

0.90

MPC

0.70

ClinPred

0.87

GERP RS

5.8

Varity_R

0.093

gMVP

0.45

Mutation Taster

=69/31

disease causing (ClinVar)

(source)

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

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rs1555352529

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over