dbSNP rs1131690776: NEK1:p.Cys276Phe (chr4-169580883-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001199397.3(NEK1):c.827G>T(p.Cys276Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NEK1
NM_001199397.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24515417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK1	NM_001199397.3 link	c.827G>T	p.Cys276Phe	missense_variant	Exon 11 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.827G>T	p.Cys276Phe	missense_variant	Exon 11 of 36	1	NM_001199397.3	ENSP00000424757.2		Q96PY6-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1377332

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

679588

African (AFR)

AF:

0.00

AC:

AN:

30982

American (AMR)

AF:

0.00

AC:

AN:

34244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24920

East Asian (EAS)

AF:

0.00

AC:

AN:

35234

South Asian (SAS)

AF:

0.00

AC:

AN:

75936

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1063948

Other (OTH)

AF:

0.00

AC:

AN:

57206

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Motor neuron disease

Uncertain:1

Aug 31, 2016

Centre for Genomic and Experimental Medicine, University of Edinburgh

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:case-control

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Benign

0.93

DEOGEN2

Uncertain

0.44

T;.;.;.;.

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

D;D;D;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.25

T;T;T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.4

M;M;M;M;M

PhyloP100

1.4

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.7

D;D;D;D;D

REVEL

Benign

0.095

Sift

Benign

0.43

T;T;T;T;T

Sift4G

Benign

0.71

T;T;T;T;T

Polyphen

0.94

P;.;D;D;D

Vest4

0.24

MutPred

0.32

Loss of catalytic residue at L277 (P = 0.0201);Loss of catalytic residue at L277 (P = 0.0201);Loss of catalytic residue at L277 (P = 0.0201);Loss of catalytic residue at L277 (P = 0.0201);Loss of catalytic residue at L277 (P = 0.0201);

MVP

0.42

MPC

0.33

ClinPred

0.94

GERP RS

5.1

Varity_R

0.60

gMVP

0.52

Mutation Taster

=93/7

polymorphism

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over