4-169580851-G-T

Position:

• chr4-169580851-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001199397.3(NEK1):​c.859C>A​(p.Pro287Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEK1 NM_001199397.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1785453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK1	NM_001199397.3	c.859C>A	p.Pro287Thr	missense_variant	11/36	ENST00000507142.6	NP_001186326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK1	ENST00000507142.6	c.859C>A	p.Pro287Thr	missense_variant	11/36	1	NM_001199397.3	ENSP00000424757	A2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1377246 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 680156

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

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.82
DEOGEN2	Benign	0.11	T;.;.;.;.
Eigen	Benign	0.063
Eigen_PC	Benign	0.085
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.92	D;D;D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.4	M;M;M;M;M
MutationTaster	Benign	0.66	D;D;D;D;D
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0080	D;D;D;D;D
Sift4G	Benign	0.14	T;T;T;T;T
Polyphen		0.56	P;.;P;P;P
Vest4		0.13
MutPred		0.27		Loss of ubiquitination at K291 (P = 0.0949);Loss of ubiquitination at K291 (P = 0.0949);Loss of ubiquitination at K291 (P = 0.0949);Loss of ubiquitination at K291 (P = 0.0949);Loss of ubiquitination at K291 (P = 0.0949);
MVP		0.75
MPC		0.069
ClinPred		0.51	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.12
gMVP		0.38

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: rs35222922; hg19: chr4-170502002; COSMIC: COSV71457464; COSMIC: COSV71457464;