rs202115635

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PP3_StrongPP5_Very_Strong

The NM_001440624.1(NEK1):c.-141C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000517 in 1,547,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic,other (★★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

NEK1
NM_001440624.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Pathogenic; other criteria provided, multiple submitters, no conflicts P:2O:1

Conservation

PhyloP100: 4.78

Publications

6 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: Pathogenic. The variant received 12 ACMG points.

PP3

BayesDel_addAF computational evidence supports a deleterious effect, 0.49

PP5

Variant 4-169588719-G-A is Pathogenic according to our data. Variant chr4-169588719-G-A is described in ClinVar as Pathogenic|other. ClinVar VariationId is 266058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001440624.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NEK1	NM_001199397.3	MANE Select	c.481C>T	p.Arg161*	stop_gained	Exon 8 of 36	NP_001186326.1
NEK1	NM_001440624.1		c.-141C>T		5_prime_UTR_premature_start_codon_gain	Exon 7 of 34	NP_001427553.1
NEK1	NM_001440625.1		c.-141C>T		5_prime_UTR_premature_start_codon_gain	Exon 7 of 33	NP_001427554.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NEK1	ENST00000507142.6	TSL:1 MANE Select	c.481C>T	p.Arg161*	stop_gained	Exon 8 of 36	ENSP00000424757.2
NEK1	ENST00000439128.6	TSL:1	c.481C>T	p.Arg161*	stop_gained	Exon 7 of 34	ENSP00000408020.2
NEK1	ENST00000511633.5	TSL:1	c.481C>T	p.Arg161*	stop_gained	Exon 8 of 35	ENSP00000423332.1

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000114

AC:

AN:

158166

AF XY:

0.000132

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000810

Gnomad ASJ exome

AF:

0.00164

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000324

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000502

AC:

AN:

1395086

Hom.:

Cov.:

AF XY:

0.0000683

AC XY:

AN XY:

688444

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31520

American (AMR)

AF:

0.0000560

AC:

AN:

35712

Ashkenazi Jewish (ASJ)

AF:

0.00183

AC:

AN:

25132

East Asian (EAS)

AF:

0.00

AC:

AN:

35682

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.0000140

AC:

AN:

1074988

Other (OTH)

AF:

0.000104

AC:

AN:

57896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.407

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41514

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67968

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

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:

0.0000628

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000615

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic; other

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

NEK1-related disorder (1)

Short-rib thoracic dysplasia 6 with or without polydactyly (1)

Motor neuron disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.49

BayesDel_noAF

Pathogenic

0.63

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.95

PhyloP100

4.8

Vest4

0.90

GERP RS

5.2

Mutation Taster

=2/198

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over