rs879253775

Positions:

• chr14-75120534-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_033116.6(NEK9):​c.500T>C​(p.Ile167Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEK9 NM_033116.6 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.70

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.95
• PP5: Variant 14-75120534-A-G is Pathogenic according to our data. Variant chr14-75120534-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 243002.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-75120534-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK9	NM_033116.6	c.500T>C	p.Ile167Thr	missense_variant	4/22	ENST00000238616.10	NP_149107.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK9	ENST00000238616.10	c.500T>C	p.Ile167Thr	missense_variant	4/22	1	NM_033116.6	ENSP00000238616	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Nevus comedonicus syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 12, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;T;.
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Uncertain	0.10	D
MutationAssessor	Uncertain	2.7	M;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0020	D;.;D
Polyphen		1.0	D;.;.
Vest4		0.96
MutPred		0.85		Loss of stability (P = 0.028);.;.;
MVP		0.90
MPC		2.3
ClinPred		0.98	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.83

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: rs879253775; hg19: chr14-75587237; COSMIC: COSV99463581; COSMIC: COSV99463581;