rs3809797

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_178170.3(NEK8):c.1170T>C(p.Gly390Gly) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. G390G) has been classified as Uncertain significance.

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:6

Conservation

PhyloP100: -3.04

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

renal-hepatic-pancreatic dysplasia 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, G2P
autosomal dominant polycystic kidney disease
Inheritance: AD Classification: STRONG Submitted by: ClinGen
nephronophthisis 9
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
polycystic kidney disease 8
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
nephronophthisis 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
renal-hepatic-pancreatic dysplasia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NEK8 links:

ENSG00000265073 (HGNC:):

ENSG00000265073 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.142).

BP6

Variant 17-28738193-T-C is Benign according to our data. Variant chr17-28738193-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178170.3. 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
	NEK8	NM_178170.3	MANE Select	c.1170T>C	p.Gly390Gly	synonymous	Exon 8 of 15	NP_835464.1	Q86SG6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NEK8	ENST00000268766.11	TSL:1 MANE Select	c.1170T>C	p.Gly390Gly	synonymous	Exon 8 of 15	ENSP00000268766.6	Q86SG6
NEK8	ENST00000969681.1		c.1209T>C	p.Gly403Gly	synonymous	Exon 8 of 15	ENSP00000639740.1
NEK8	ENST00000903448.1		c.1038T>C	p.Gly346Gly	synonymous	Exon 7 of 14	ENSP00000573507.1

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

GnomAD2 exomes

AF:

0.128

AC:

32057

AN:

251116

AF XY:

0.127

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 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

African (AFR)

AF:

0.346

AC:

11580

AN:

33480

American (AMR)

AF:

0.0788

AC:

3525

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

3511

AN:

26134

East Asian (EAS)

AF:

0.206

AC:

8192

AN:

39700

South Asian (SAS)

AF:

0.208

AC:

17966

AN:

86252

European-Finnish (FIN)

AF:

0.0841

AC:

4492

AN:

53416

Middle Eastern (MID)

AF:

0.159

AC:

916

AN:

5764

European-Non Finnish (NFE)

AF:

0.0884

AC:

98296

AN:

1111986

Other (OTH)

AF:

0.120

AC:

7261

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

8801

17602

26403

35204

44005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3922

7844

11766

15688

19610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.165

AC:

25034

AN:

152098

Hom.:

2890

Cov.:

AF XY:

0.165

AC XY:

12251

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.323

AC:

13387

AN:

41446

American (AMR)

AF:

0.116

AC:

1768

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

465

AN:

3472

East Asian (EAS)

AF:

0.183

AC:

944

AN:

5154

South Asian (SAS)

AF:

0.216

AC:

1042

AN:

4826

European-Finnish (FIN)

AF:

0.0843

AC:

894

AN:

10600

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0891

AC:

6060

AN:

67982

Other (OTH)

AF:

0.142

AC:

300

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1004

2009

3013

4018

5022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

274

548

822

1096

1370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.117

Hom.:

1560

Bravo

AF:

0.171

Asia WGS

AF:

0.199

AC:

693

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nephronophthisis 9 (2)

not provided (2)

not specified (1)

Renal-hepatic-pancreatic dysplasia 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.6

(source)

DANN

Benign

0.53

PhyloP100

-3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over