Variant 17-28740987-TGAG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_178170.3(NEK8):c.1732+8_1732+10delGGA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00304 in 1,614,112 control chromosomes in the GnomAD database, including 133 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 124 hom. )

Consequence

NEK8
NM_178170.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.81

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:

ENSG00000265073 (HGNC:):

ENSG00000265073 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 17-28740987-TGAG-T is Benign according to our data. Variant chr17-28740987-TGAG-T is described in ClinVar as [Likely_benign]. Clinvar id is 242154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK8	NM_178170.3 linkuse as main transcript	c.1732+8_1732+10delGGA		splice_region_variant, intron_variant		ENST00000268766.11	NP_835464.1	Q86SG6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
NEK8	ENST00000268766.11 linkuse as main transcript	c.1732+8_1732+10delGGA	splice_region_variant, intron_variant	1	NM_178170.3	ENSP00000268766.6	Q86SG6
NEK8	ENST00000543014.1 linkuse as main transcript	n.119-506_119-504delGGA	intron_variant	2		ENSP00000465859.1	K7EL04
ENSG00000265073	ENST00000584779.1 linkuse as main transcript	n.417+1359_417+1361delCTC	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00351

AC:

534

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0663

Gnomad SAS

AF:

0.00643

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00831

AC:

2089

AN:

251356

Hom.:

AF XY:

0.00703

AC XY:

955

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0195

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.0690

Gnomad SAS exome

AF:

0.00203

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000343

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00299

AC:

4377

AN:

1461852

Hom.:

124

AF XY:

0.00292

AC XY:

2125

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0170

Gnomad4 ASJ exome

AF:

0.00142

Gnomad4 EAS exome

AF:

0.0716

Gnomad4 SAS exome

AF:

0.00241

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.000256

Gnomad4 OTH exome

AF:

0.00381

GnomAD4 genome

AF:

0.00349

AC:

531

AN:

152260

Hom.:

Cov.:

AF XY:

0.00398

AC XY:

296

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00621

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0660

Gnomad4 SAS

AF:

0.00664

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00193

Hom.:

Bravo

AF:

0.00499

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Kidney disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 12, 2016

- -

Nephronophthisis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Nephronophthisis 9;C3809434:Renal-hepatic-pancreatic dysplasia 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 29, 2021

- -

Nephronophthisis 9

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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