Genetic Variant NM_003157.6:c.*706A>G (chr3-52711071-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003157.6(NEK4):c.*706A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,464 control chromosomes in the GnomAD database, including 12,688 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 0.39 ( 12649 hom., cov: 33)

Exomes 𝑓: 0.42 ( 39 hom. )

Consequence

NEK4
NM_003157.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.704

Publications

22 publications found

Variant links:

Genes affected

NEK4 (HGNC:11399): (NIMA related kinase 4) The protein encoded by this gene is a serine/threonine protein kinase required for normal entry into replicative senescence. The encoded protein also is involved in cell cycle arrest in response to double-stranded DNA damage. Finally, this protein plays a role in maintaining cilium integrity, and defects in this gene have been associated with ciliopathies. [provided by RefSeq, Jan 2017]

NEK4 links:

SPCS1 (HGNC:23401): (signal peptidase complex subunit 1) Predicted to enable peptidase activity and ribosome binding activity. Involved in viral protein processing and virion assembly. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPCS1 links:

Genome browser will be placed here

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=-0.74).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003157.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEK4	NM_003157.6	MANE Select	c.*706A>G	3_prime_UTR	Exon 16 of 16	NP_003148.2	P51957-1
SPCS1	NM_014041.5	MANE Select	c.*3259T>C	3_prime_UTR	Exon 4 of 4	NP_054760.4	A0A5F9YFS9
NEK4	NM_001348412.2		c.*706A>G	3_prime_UTR	Exon 15 of 15	NP_001335341.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEK4	ENST00000233027.10	TSL:1 MANE Select	c.*706A>G	3_prime_UTR	Exon 16 of 16	ENSP00000233027.5	P51957-1
SPCS1	ENST00000619898.5	TSL:1 MANE Select	c.*3259T>C	3_prime_UTR	Exon 4 of 4	ENSP00000478310.2	A0A5F9YFS9
NEK4	ENST00000944576.1		c.*706A>G	3_prime_UTR	Exon 16 of 16	ENSP00000614635.1

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59721

AN:

151922

Hom.:

12652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.355

Gnomad ASJ

AF:

0.434

Gnomad EAS

AF:

0.543

Gnomad SAS

AF:

0.657

Gnomad FIN

AF:

0.483

Gnomad MID

AF:

0.378

Gnomad NFE

AF:

0.442

Gnomad OTH

AF:

0.396

GnomAD4 exome

AF:

0.422

AC:

178

AN:

422

Hom.:

Cov.:

AF XY:

0.418

AC XY:

107

AN XY:

256

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.421

AC:

175

AN:

416

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.393

AC:

59735

AN:

152042

Hom.:

12649

Cov.:

AF XY:

0.399

AC XY:

29671

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.250

AC:

10377

AN:

41464

American (AMR)

AF:

0.356

AC:

5431

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.434

AC:

1504

AN:

3468

East Asian (EAS)

AF:

0.543

AC:

2812

AN:

5182

South Asian (SAS)

AF:

0.657

AC:

3172

AN:

4828

European-Finnish (FIN)

AF:

0.483

AC:

5094

AN:

10544

Middle Eastern (MID)

AF:

0.370

AC:

108

AN:

292

European-Non Finnish (NFE)

AF:

0.443

AC:

30075

AN:

67964

Other (OTH)

AF:

0.393

AC:

831

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1762

3523

5285

7046

8808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.413

Hom.:

1719

Bravo

AF:

0.373

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.70

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over