Genetic Variant NM_002498.3:c.*402G>A (chr13-52132740-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.88

Publications

1 publications found

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:

ENSG00000273523 (HGNC:):

ENSG00000273523 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002498.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NEK3	NM_002498.3	MANE Select	c.*402G>A	3_prime_UTR	Exon 16 of 16	NP_002489.1
NEK3	NR_164641.1		n.1985G>A	non_coding_transcript_exon	Exon 15 of 15
NEK3	NM_001424264.1		c.*402G>A	3_prime_UTR	Exon 16 of 16	NP_001411193.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NEK3	ENST00000610828.5	TSL:1 MANE Select	c.*402G>A	3_prime_UTR	Exon 16 of 16	ENSP00000480328.1
NEK3	ENST00000550331.1	TSL:2	n.638G>A	non_coding_transcript_exon	Exon 2 of 2
NEK3	ENST00000617054.1	TSL:5	n.*976G>A	non_coding_transcript_exon	Exon 14 of 14	ENSP00000484594.1

Frequencies

GnomAD3 genomes

AF:

0.0156

AC:

2379

AN:

152108

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0157

AC XY:

100

AN XY:

6352

show subpopulations

African (AFR)

AF:

0.00591

AC:

AN:

508

American (AMR)

AF:

0.106

AC:

121

AN:

1146

Ashkenazi Jewish (ASJ)

AF:

0.00670

AC:

AN:

448

East Asian (EAS)

AF:

0.00

AC:

AN:

718

South Asian (SAS)

AF:

0.0149

AC:

AN:

536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00977

AC:

AN:

8090

Other (OTH)

AF:

0.0112

AC:

AN:

714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0157

AC:

2384

AN:

152226

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

1228

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.00638

AC:

265

AN:

41532

American (AMR)

AF:

0.0809

AC:

1237

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3472

East Asian (EAS)

AF:

0.000965

AC:

AN:

5180

South Asian (SAS)

AF:

0.0112

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0108

AC:

732

AN:

68012

Other (OTH)

AF:

0.0128

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

114

229

343

458

572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0209

Hom.:

Bravo

AF:

0.0212

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.015

(source)

DANN

Benign

0.58

PhyloP100

-4.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over