rs1555563787

Positions:

• chr17-28734777-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The ENST00000268766.11(NEK8):​c.259A>G​(p.Thr87Ala) 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: NEK8 ENST00000268766.11 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.79

Genes affected

NEK8 (HGNC:13387): (NIMA related kinase 8) This gene encodes a member of the serine/threionine protein kinase family related to NIMA (never in mitosis, gene A) of Aspergillus nidulans. The encoded protein may play a role in cell cycle progression from G2 to M phase. Mutations in the related mouse gene are associated with a disease phenotype that closely parallels the juvenile autosomal recessive form of polycystic kidney disease in humans. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.793
• PP5: Variant 17-28734777-A-G is Pathogenic according to our data. Variant chr17-28734777-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 490179.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK8	NM_178170.3	c.259A>G	p.Thr87Ala	missense_variant	3/15	ENST00000268766.11	NP_835464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK8	ENST00000268766.11	c.259A>G	p.Thr87Ala	missense_variant	3/15	1	NM_178170.3	ENSP00000268766	P1
	ENST00000584779.1	n.418-1790T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Renal-hepatic-pancreatic dysplasia 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T;T;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.79	D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	.;.;L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-4.2	.;.;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0060	.;.;D
Sift4G	Uncertain	0.034	D;D;D
Polyphen		0.99	.;.;D
Vest4		0.87
MutPred		0.61		.;.;Loss of sheet (P = 0.302);
MVP		0.84
MPC		0.94
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.43

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: rs1555563787; hg19: chr17-27061795;