rs1886541

Variant names:

• chr13-52132638-A-G
• rs1886541
• ENST00000613982.1:n.3348A>G

Variant summary

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

The ENST00000613982.1(ENSG00000273523):​n.3348A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 152,554 control chromosomes in the GnomAD database, including 73 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 (73 hom., cov: 32)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: ENSG00000273523 ENST00000613982.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

Genes affected

ENSG00000273523 (HGNC:):

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK3	NM_002498.3	c.*504T>C		downstream_gene_variant		ENST00000610828.5	NP_002489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK3	ENST00000610828.5	c.*504T>C		downstream_gene_variant		1	NM_002498.3	ENSP00000480328.1

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2375 AN: 152194 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.00630

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0811

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.0207 AC: 5 AN: 242 Hom.: 0 Cov.: 0 AF XY: 0.0339 AC XY: 4 AN XY: 118

Gnomad4 AMR exome AF: 0.0833

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00610

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0156 AC: 2380 AN: 152312 Hom.: 73 Cov.: 32 AF XY: 0.0164 AC XY: 1225 AN XY: 74478

Gnomad4 AFR AF: 0.00635

Gnomad4 AMR AF: 0.0809

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0155 Hom.: 59

Bravo AF: 0.0213

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	-0.84
CADD	Benign	2.2
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1886541; hg19: chr13-52706774;