rs1131690776

chr4-169580883-C-Achr4-169580883-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001199397.3(NEK1):c.827G>T(p.Cys276Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24515417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK1	NM_001199397.3	c.827G>T	p.Cys276Phe	missense_variant	11/36	ENST00000507142.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK1	ENST00000507142.6	c.827G>T	p.Cys276Phe	missense_variant	11/36	1	NM_001199397.3	A2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1377332 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 679588

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Motor neuron disease Uncertain:1

Uncertain significance, criteria provided, single submitter

case-control

Centre for Genomic and Experimental Medicine, University of Edinburgh

Aug 31, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Uncertain	23
Dann	Benign	0.93
DEOGEN2	Uncertain	0.44	T;.;.;.;.
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D;D;D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.25	T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.4	M;M;M;M;M
MutationTaster	Benign	0.97	D;D;D;D;D
PrimateAI	Benign	0.48	T
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	D
GERP RS		5.1
Varity_R		0.60
gMVP		0.52

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

LitVar

Other links and lift over

dbSNP: rs1131690776; hg19: chr4-170502034;