rs2296351

chr13-52135802-A-Cchr13-52135802-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002498.3(NEK3):c.1236T>G(p.Pro412=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,613,036 control chromosomes in the GnomAD database, including 102,043 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 0.27 (7008 hom., cov: 32)
  • Exomes 𝑓: 0.35 (95035 hom.)
• Consequence: NEK3 NM_002498.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-0.395 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK3	NM_002498.3	c.1236T>G	p.Pro412=	synonymous_variant	14/16	ENST00000610828.5
NEK3	NM_152720.3	c.1236T>G	p.Pro412=	synonymous_variant	14/16
NEK3	NR_164641.1	n.1298T>G		non_coding_transcript_exon_variant	13/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK3	ENST00000610828.5	c.1236T>G	p.Pro412=	synonymous_variant	14/16	1	NM_002498.3	P2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41451 AN: 151998 Hom.: 7012 Cov.: 32

Gnomad AFR AF: 0.0681

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.324

GnomAD3 exomes AF: 0.305 AC: 75954 AN: 248640 Hom.: 12802 AF XY: 0.307 AC XY: 41433 AN XY: 134960

Gnomad AFR exome AF: 0.0613

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.374

Gnomad EAS exome AF: 0.209

Gnomad SAS exome AF: 0.191

Gnomad FIN exome AF: 0.361

Gnomad NFE exome AF: 0.373

Gnomad OTH exome AF: 0.348

GnomAD4 exome AF: 0.352 AC: 514816 AN: 1460920 Hom.: 95035 Cov.: 34 AF XY: 0.348 AC XY: 253100 AN XY: 726790

Gnomad4 AFR exome AF: 0.0572

Gnomad4 AMR exome AF: 0.287

Gnomad4 ASJ exome AF: 0.381

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.369

Gnomad4 NFE exome AF: 0.382

Gnomad4 OTH exome AF: 0.344

GnomAD4 genome AF: 0.272 AC: 41439 AN: 152116 Hom.: 7008 Cov.: 32 AF XY: 0.269 AC XY: 20025 AN XY: 74358

Gnomad4 AFR AF: 0.0679

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.322

Alfa AF: 0.325 Hom.: 7883

Bravo AF: 0.264

Asia WGS AF: 0.162 AC: 563 AN: 3478

EpiCase AF: 0.368

EpiControl AF: 0.377

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.83
Dann	Benign	0.39

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: rs2296351; hg19: chr13-52709938; COSMIC: COSV51616106; COSMIC: COSV51616106;