4-169477252-T-G

Position:

• chr4-169477252-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001199397.3(NEK1):​c.2306A>C​(p.His769Pro) 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. 16/21 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: 32)
• Consequence: NEK1 NM_001199397.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06214243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEK1	NM_001199397.3	c.2306A>C	p.His769Pro	missense_variant	26/36	ENST00000507142.6	NP_001186326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK1	ENST00000507142.6	c.2306A>C	p.His769Pro	missense_variant	26/36	1	NM_001199397.3	ENSP00000424757.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	1.1
DANN	Benign	0.17
DEOGEN2	Benign	0.060	T;.;.;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.47	T;T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.062	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L;.;.;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.20	T;T;T;T;T
Sift4G	Benign	0.23	T;T;T;T;T
Polyphen		0.0	B;.;B;B;B
Vest4		0.14
MutPred		0.093		Gain of loop (P = 0.1069);.;.;.;.;
MVP		0.41
MPC		0.078
ClinPred		0.031	T
GERP RS		-0.23
Varity_R		0.089
gMVP		0.31

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: rs375173827; hg19: chr4-170398403;