rs1886540

chr13-52132740-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002498.3(NEK3):c.*402G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 164,834 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (75 hom., cov: 32)
  • Exomes 𝑓: 0.018 (8 hom.)
• Consequence: NEK3 NM_002498.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.88

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK3	NM_002498.3	c.*402G>A		3_prime_UTR_variant	16/16	ENST00000610828.5
NEK3	NM_152720.3	c.*402G>A		3_prime_UTR_variant	16/16
NEK3	NR_164641.1	n.1985G>A		non_coding_transcript_exon_variant	15/15
LOC101929657	NR_110306.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK3	ENST00000610828.5	c.*402G>A		3_prime_UTR_variant	16/16	1	NM_002498.3	P2
	ENST00000613982.1			downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2379 AN: 152108 Hom.: 76 Cov.: 32

Gnomad AFR AF: 0.00633

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0812

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.0176 AC: 222 AN: 12608 Hom.: 8 Cov.: 0 AF XY: 0.0157 AC XY: 100 AN XY: 6352

Gnomad4 AFR exome AF: 0.00591

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.00670

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0149

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00977

Gnomad4 OTH exome AF: 0.0112

GnomAD4 genome AF: 0.0157 AC: 2384 AN: 152226 Hom.: 75 Cov.: 32 AF XY: 0.0165 AC XY: 1228 AN XY: 74424

Gnomad4 AFR AF: 0.00638

Gnomad4 AMR AF: 0.0809

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.00170

Gnomad4 NFE AF: 0.0108

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0220 Hom.: 45

Bravo AF: 0.0212

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.015
Dann	Benign	0.58

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: rs1886540; hg19: chr13-52706876;