rs3809797

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_178170.3(NEK8):c.1170T>C(p.Gly390=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,613,942 control chromosomes in the GnomAD database, including 13,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2890 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10426 hom. )

Consequence

NEK8
NM_178170.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.04

Variant links:

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]

NEK8 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 17-28738193-T-C is Benign according to our data. Variant chr17-28738193-T-C is described in ClinVar as [Benign]. Clinvar id is 262928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK8	NM_178170.3 linkuse as main transcript	c.1170T>C	p.Gly390=	synonymous_variant	8/15	ENST00000268766.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NEK8	ENST00000268766.11 linkuse as main transcript	c.1170T>C	p.Gly390=	synonymous_variant	8/15	1	NM_178170.3	P1
	ENST00000584779.1 linkuse as main transcript	n.417+4156A>G		intron_variant, non_coding_transcript_variant		5
NEK8	ENST00000592510.1 linkuse as main transcript	c.732T>C	p.Gly244=	synonymous_variant	5/5	3
NEK8	ENST00000543014.1 linkuse as main transcript	c.1330T>C	p.Cys444Arg	missense_variant, NMD_transcript_variant	7/11	2

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

25000

AN:

151978

Hom.:

2885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.323

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.0843

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.0891

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.128

AC:

32057

AN:

251116

Hom.:

2752

AF XY:

0.127

AC XY:

17255

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.332

Gnomad AMR exome

AF:

0.0744

Gnomad ASJ exome

AF:

0.135

Gnomad EAS exome

AF:

0.197

Gnomad SAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.0873

Gnomad NFE exome

AF:

0.0888

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.107

AC:

155739

AN:

1461844

Hom.:

10426

Cov.:

AF XY:

0.109

AC XY:

79135

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.346

Gnomad4 AMR exome

AF:

0.0788

Gnomad4 ASJ exome

AF:

0.134

Gnomad4 EAS exome

AF:

0.206

Gnomad4 SAS exome

AF:

0.208

Gnomad4 FIN exome

AF:

0.0841

Gnomad4 NFE exome

AF:

0.0884

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.165

AC:

25034

AN:

152098

Hom.:

2890

Cov.:

AF XY:

0.165

AC XY:

12251

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.323

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.134

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.216

Gnomad4 FIN

AF:

0.0843

Gnomad4 NFE

AF:

0.0891

Gnomad4 OTH

AF:

0.142

Alfa

AF:

0.119

Hom.:

1260

Bravo

AF:

0.171

Asia WGS

AF:

0.199

AC:

693

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephronophthisis 9

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Renal-hepatic-pancreatic dysplasia 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.6

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over