Variant 4-169561898-TA-TAA 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_001199397.3(NEK1):c.1081-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 1,588,998 control chromosomes in the GnomAD database, including 4,075 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 0.088 ( 755 hom., cov: 30)

Exomes 𝑓: 0.065 ( 3320 hom. )

Consequence

NEK1
NM_001199397.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:8

Conservation

PhyloP100: -1.82

Variant links:

Genes affected

NEK1 (HGNC:7744): (NIMA related kinase 1) The protein encoded by this gene is a serine/threonine kinase involved in cell cycle regulation. The encoded protein is found in a centrosomal complex with FEZ1, a neuronal protein that plays a role in axonal development. Defects in this gene are a cause of polycystic kidney disease (PKD). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

NEK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 4-169561898-T-TA is Benign according to our data. Variant chr4-169561898-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 95506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK1	NM_001199397.3 link	c.1081-8dupT		splice_region_variant, intron_variant	Intron 13 of 35	ENST00000507142.6	NP_001186326.1	Q96PY6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK1	ENST00000507142.6 link	c.1081-8_1081-7insT		splice_region_variant, intron_variant	Intron 13 of 35	1	NM_001199397.3	ENSP00000424757.2		Q96PY6-3

Frequencies

GnomAD3 genomes

AF:

0.0881

AC:

13298

AN:

150992

Hom.:

753

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.0672

Gnomad AMR

AF:

0.0533

Gnomad ASJ

AF:

0.0761

Gnomad EAS

AF:

0.0286

Gnomad SAS

AF:

0.0827

Gnomad FIN

AF:

0.0666

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0623

Gnomad OTH

AF:

0.0745

GnomAD3 exomes

AF:

0.0681

AC:

15532

AN:

228056

Hom.:

605

AF XY:

0.0672

AC XY:

8342

AN XY:

124178

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.0367

Gnomad ASJ exome

AF:

0.0802

Gnomad EAS exome

AF:

0.0258

Gnomad SAS exome

AF:

0.0863

Gnomad FIN exome

AF:

0.0686

Gnomad NFE exome

AF:

0.0657

Gnomad OTH exome

AF:

0.0675

GnomAD4 exome

AF:

0.0647

AC:

92972

AN:

1437890

Hom.:

3320

Cov.:

AF XY:

0.0645

AC XY:

46134

AN XY:

715006

show subpopulations

Gnomad4 AFR exome

AF:

0.161

Gnomad4 AMR exome

AF:

0.0394

Gnomad4 ASJ exome

AF:

0.0782

Gnomad4 EAS exome

AF:

0.0270

Gnomad4 SAS exome

AF:

0.0867

Gnomad4 FIN exome

AF:

0.0710

Gnomad4 NFE exome

AF:

0.0617

Gnomad4 OTH exome

AF:

0.0697

GnomAD4 genome

AF:

0.0881

AC:

13312

AN:

151108

Hom.:

755

Cov.:

AF XY:

0.0881

AC XY:

6500

AN XY:

73812

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.0533

Gnomad4 ASJ

AF:

0.0761

Gnomad4 EAS

AF:

0.0287

Gnomad4 SAS

AF:

0.0835

Gnomad4 FIN

AF:

0.0666

Gnomad4 NFE

AF:

0.0623

Gnomad4 OTH

AF:

0.0738

Bravo

AF:

0.0910

Asia WGS

AF:

0.0640

AC:

221

AN:

3446

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Apr 11, 2013

Eurofins Ntd Llc (ga)

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 28, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Short-rib thoracic dysplasia 6 with or without polydactyly

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Short rib-polydactyly syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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