rs140408058

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001199397.3(NEK1):c.3285C>T(p.Pro1095Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000634 in 1,609,494 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00039 ( 2 hom. )

Consequence

NEK1
NM_001199397.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.53

Publications

0 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 4-169406685-G-A is Benign according to our data. Variant chr4-169406685-G-A is described in ClinVar as Benign. ClinVar VariationId is 457136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.53 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00296 (450/152040) while in subpopulation AFR AF = 0.0101 (419/41510). AF 95% confidence interval is 0.0093. There are 1 homozygotes in GnomAd4. There are 207 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK1	NM_001199397.3 link	c.3285C>T	p.Pro1095Pro	synonymous_variant	Exon 32 of 36	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.3285C>T	p.Pro1095Pro	synonymous_variant	Exon 32 of 36	1	NM_001199397.3	ENSP00000424757.2		Q96PY6-3

Frequencies

GnomAD3 genomes

AF:

0.00294

AC:

446

AN:

151922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00105

AC:

259

AN:

246800

AF XY:

0.000821

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.00190

Gnomad ASJ exome

AF:

0.000498

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.000391

AC:

570

AN:

1457454

Hom.:

Cov.:

AF XY:

0.000352

AC XY:

255

AN XY:

725052

show subpopulations

African (AFR)

AF:

0.00976

AC:

325

AN:

33304

American (AMR)

AF:

0.00183

AC:

AN:

44334

Ashkenazi Jewish (ASJ)

AF:

0.000422

AC:

AN:

26064

East Asian (EAS)

AF:

0.00

AC:

AN:

39510

South Asian (SAS)

AF:

0.0000468

AC:

AN:

85458

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53350

Middle Eastern (MID)

AF:

0.000869

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000586

AC:

AN:

1109486

Other (OTH)

AF:

0.00131

AC:

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

105

131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00296

AC:

450

AN:

152040

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

207

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.0101

AC:

419

AN:

41510

American (AMR)

AF:

0.00105

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10528

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67980

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00145

Hom.:

Bravo

AF:

0.00326

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000165

EpiControl

AF:

0.000299

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 30, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Short-rib thoracic dysplasia 6 with or without polydactyly

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This 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. -

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

NEK1-related disorder

Benign:1

Apr 01, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.2

(source)

DANN

Benign

0.39

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over