Menu
GeneBe

rs145898152

Variant summary

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

The NM_178170.3(NEK8):c.2052G>A(p.Ser684=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,614,048 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 9 hom., cov: 32)
Exomes 𝑓: 0.0017 ( 69 hom. )

Consequence

NEK8
NM_178170.3 splice_region, synonymous

Scores

2
Splicing: ADA: 0.00001877
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -10.2
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]

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=-0.98).
BP6
Variant 17-28741960-G-A is Benign according to our data. Variant chr17-28741960-G-A is described in ClinVar as [Benign]. Clinvar id is 194569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-28741960-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-10.2 with no splicing effect.
BA1
GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NEK8NM_178170.3 linkuse as main transcriptc.2052G>A p.Ser684= splice_region_variant, synonymous_variant 15/15 ENST00000268766.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NEK8ENST00000268766.11 linkuse as main transcriptc.2052G>A p.Ser684= splice_region_variant, synonymous_variant 15/151 NM_178170.3 P1
ENST00000584779.1 linkuse as main transcriptn.417+389C>T intron_variant, non_coding_transcript_variant 5
NEK8ENST00000543014.1 linkuse as main transcriptc.*193G>A splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant 11/112

Frequencies

GnomAD3 genomes
AF:
0.00301
AC:
458
AN:
152106
Hom.:
10
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000990
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0264
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00768
AC:
1928
AN:
250890
Hom.:
58
AF XY:
0.00579
AC XY:
785
AN XY:
135692
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.0549
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00375
GnomAD4 exome
AF:
0.00166
AC:
2429
AN:
1461824
Hom.:
69
Cov.:
31
AF XY:
0.00140
AC XY:
1018
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.000478
Gnomad4 AMR exome
AF:
0.0521
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.00108
GnomAD4 genome
AF:
0.00300
AC:
457
AN:
152224
Hom.:
9
Cov.:
32
AF XY:
0.00347
AC XY:
258
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.000987
Gnomad4 AMR
AF:
0.0263
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00427
Alfa
AF:
0.000202
Hom.:
0
Bravo
AF:
0.00514
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Nephronophthisis 9 Benign:2
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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. -
Benign, criteria provided, single submitterclinical testingInvitaeJan 25, 2024- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Feb 08, 2017- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxSep 02, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
Cadd
Benign
0.0010
Dann
Benign
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000019
dbscSNV1_RF
Benign
0.012
SpliceAI score (max)
0.080
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.

Other links and lift over

dbSNP: rs145898152; hg19: chr17-27068978; API