13-52151194-T-A

Variant names:

• chr13-52151194-T-A
• NM_002498.3:c.500A>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002498.3(NEK3):​c.500A>T​(p.Tyr167Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NEK3 NM_002498.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.64

Genes affected

NEK3 (HGNC:7746): (NIMA related kinase 3) This gene encodes a member of the NimA (never in mitosis A) family of serine/threonine protein kinases. The encoded protein differs from other NimA family members in that it is not cell cycle regulated and is found primarily in the cytoplasm. The kinase is activated by prolactin stimulation, leading to phosphorylation of VAV2 guanine nucleotide exchange factor, paxillin, and activation of the RAC1 GTPase. Two functional alleles for this gene have been identified in humans. The reference genome assembly (GRCh38) represents a functional allele that is associated with the inclusion of an additional coding exon in protein-coding transcripts, compared to an alternate functional allele that lacks the exon. [provided by RefSeq, Sep 2019]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK3	NM_002498.3	c.500A>T	p.Tyr167Phe	missense_variant	Exon 7 of 16	ENST00000610828.5	NP_002489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK3	ENST00000610828.5	c.500A>T	p.Tyr167Phe	missense_variant	Exon 7 of 16	1	NM_002498.3	ENSP00000480328.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	.;.;T;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D;D;D;.
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.80	D;D;D;D
MetaSVM	Uncertain	-0.090	T
MutationAssessor	Benign	0.78	.;N;N;N
PrimateAI	Uncertain	0.69	T
Sift4G	Uncertain	0.048	D;D;D;D
Polyphen		0.97	.;.;D;D
Vest4		0.72
MVP		0.52
ClinPred		0.96	D
GERP RS		6.0
Varity_R		0.35
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-52725329;