Genetic Variant NM_014397.6:c.*434A>G (chr9-124351381-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014397.6(NEK6):c.*434A>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 0.484 in 160,860 control chromosomes in the GnomAD database, including 19,716 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 0.48 ( 18494 hom., cov: 33)

Exomes 𝑓: 0.50 ( 1222 hom. )

Consequence

NEK6
NM_014397.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.182

Publications

10 publications found

Variant links:

Genes affected

NEK6 (HGNC:7749): (NIMA related kinase 6) The protein encoded by this gene is a kinase required for progression through the metaphase portion of mitosis. Inhibition of the encoded protein can lead to apoptosis. This protein also can enhance tumorigenesis by suppressing tumor cell senescence. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

NEK6 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=-0.58).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014397.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEK6	NM_014397.6	MANE Select	c.*434A>G	3_prime_UTR	Exon 10 of 10	NP_055212.2
NEK6	NM_001145001.3		c.*434A>G	3_prime_UTR	Exon 11 of 11	NP_001138473.1	Q9HC98-2
NEK6	NM_001166171.2		c.*434A>G	3_prime_UTR	Exon 11 of 11	NP_001159643.1	Q9HC98-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEK6	ENST00000320246.10	TSL:1 MANE Select	c.*434A>G	3_prime_UTR	Exon 10 of 10	ENSP00000319734.5	Q9HC98-1
NEK6	ENST00000373600.7	TSL:1	c.*434A>G	3_prime_UTR	Exon 11 of 11	ENSP00000362702.3	Q9HC98-2
NEK6	ENST00000540326.5	TSL:1	c.*434A>G	3_prime_UTR	Exon 10 of 10	ENSP00000441469.1	Q9HC98-3

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73428

AN:

151972

Hom.:

18490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.355

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.591

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.522

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.563

Gnomad OTH

AF:

0.513

GnomAD4 exome

AF:

0.505

AC:

4426

AN:

8770

Hom.:

1222

Cov.:

AF XY:

0.488

AC XY:

2214

AN XY:

4534

show subpopulations

African (AFR)

AF:

0.311

AC:

AN:

190

American (AMR)

AF:

0.476

AC:

263

AN:

552

Ashkenazi Jewish (ASJ)

AF:

0.534

AC:

124

AN:

232

East Asian (EAS)

AF:

0.275

AC:

AN:

204

South Asian (SAS)

AF:

0.343

AC:

285

AN:

830

European-Finnish (FIN)

AF:

0.487

AC:

311

AN:

638

Middle Eastern (MID)

AF:

0.583

AC:

AN:

European-Non Finnish (NFE)

AF:

0.547

AC:

2997

AN:

5476

Other (OTH)

AF:

0.507

AC:

310

AN:

612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

101

203

304

406

507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.483

AC:

73451

AN:

152090

Hom.:

18494

Cov.:

AF XY:

0.478

AC XY:

35535

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.355

AC:

14709

AN:

41470

American (AMR)

AF:

0.512

AC:

7832

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.591

AC:

2051

AN:

3472

East Asian (EAS)

AF:

0.317

AC:

1636

AN:

5166

South Asian (SAS)

AF:

0.372

AC:

1790

AN:

4818

European-Finnish (FIN)

AF:

0.522

AC:

5515

AN:

10568

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.563

AC:

38304

AN:

67988

Other (OTH)

AF:

0.512

AC:

1083

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1937

3874

5810

7747

9684

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<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:

0.534

Hom.:

84632

Bravo

AF:

0.470

Asia WGS

AF:

0.355

AC:

1236

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.64

PhyloP100

0.18

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