4-169561898-T-TA

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis, susceptibility to, 24
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
short-rib thoracic dysplasia 6 with or without polydactyly
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
orofaciodigital syndrome type II
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
short rib-polydactyly syndrome, Majewski type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NEK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199397.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NEK1	NM_001199397.3	MANE Select	c.1081-8dupT	splice_region intron	N/A	NP_001186326.1
NEK1	NM_001374418.1		c.1081-8dupT	splice_region intron	N/A	NP_001361347.1
NEK1	NM_001374419.1		c.1081-8dupT	splice_region intron	N/A	NP_001361348.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NEK1	ENST00000507142.6	TSL:1 MANE Select	c.1081-8dupT	splice_region intron	N/A	ENSP00000424757.2
NEK1	ENST00000439128.6	TSL:1	c.1081-8dupT	splice_region intron	N/A	ENSP00000408020.2
NEK1	ENST00000511633.5	TSL:1	c.1081-8dupT	splice_region intron	N/A	ENSP00000423332.1

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

GnomAD2 exomes

AF:

0.0681

AC:

15532

AN:

228056

AF XY:

0.0672

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 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

African (AFR)

AF:

0.161

AC:

5124

AN:

31904

American (AMR)

AF:

0.0394

AC:

1616

AN:

41048

Ashkenazi Jewish (ASJ)

AF:

0.0782

AC:

1991

AN:

25470

East Asian (EAS)

AF:

0.0270

AC:

1064

AN:

39414

South Asian (SAS)

AF:

0.0867

AC:

7042

AN:

81234

European-Finnish (FIN)

AF:

0.0710

AC:

3760

AN:

52932

Middle Eastern (MID)

AF:

0.0515

AC:

287

AN:

5576

European-Non Finnish (NFE)

AF:

0.0617

AC:

67953

AN:

1100978

Other (OTH)

AF:

0.0697

AC:

4135

AN:

59334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

4264

8528

12793

17057

21321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2562

5124

7686

10248

12810

<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:

0.0881

AC:

13312

AN:

151108

Hom.:

755

Cov.:

AF XY:

0.0881

AC XY:

6500

AN XY:

73812

show subpopulations

African (AFR)

AF:

0.159

AC:

6564

AN:

41178

American (AMR)

AF:

0.0533

AC:

808

AN:

15166

Ashkenazi Jewish (ASJ)

AF:

0.0761

AC:

264

AN:

3468

East Asian (EAS)

AF:

0.0287

AC:

148

AN:

5162

South Asian (SAS)

AF:

0.0835

AC:

400

AN:

4792

European-Finnish (FIN)

AF:

0.0666

AC:

685

AN:

10290

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0623

AC:

4220

AN:

67762

Other (OTH)

AF:

0.0738

AC:

154

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

577

1154

1730

2307

2884

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<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:

0.0341

Hom.:

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

Jun 08, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

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

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

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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 v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over