Variant 13-52135802-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.395

Variant links:

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]

NEK3 links:

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ACMG classification

Classification made for transcript

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	Protein
NEK3	NM_002498.3 linkuse as main transcript	c.1236T>G	p.Pro412=	synonymous_variant	14/16	ENST00000610828.5	NP_002489.1
NEK3	NM_152720.3 linkuse as main transcript	c.1236T>G	p.Pro412=	synonymous_variant	14/16		NP_689933.1
NEK3	NR_164641.1 linkuse as main transcript	n.1298T>G		non_coding_transcript_exon_variant	13/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEK3	ENST00000610828.5 linkuse as main transcript	c.1236T>G	p.Pro412=	synonymous_variant	14/16	1	NM_002498.3	ENSP00000480328	P2	P51956-1

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41451

AN:

151998

Hom.:

7012

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.348

AC XY:

253100

AN XY:

726790

show subpopulations

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.:

AF XY:

0.269

AC XY:

20025

AN XY:

74358

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over