Genetic Variant NM_014840.3:c.513+62T>C (chr12-106086672-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_014840.3(NUAK1):c.513+62T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,524,904 control chromosomes in the GnomAD database, including 127,386 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 0.40 ( 12118 hom., cov: 32)

Exomes 𝑓: 0.41 ( 115268 hom. )

Consequence

NUAK1
NM_014840.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.687

Publications

5 publications found

Variant links:

Genes affected

NUAK1 (HGNC:14311): (NUAK family kinase 1) Enables p53 binding activity and protein serine/threonine kinase activity. Involved in several processes, including protein phosphorylation; regulation of cellular senescence; and regulation of myosin-light-chain-phosphatase activity. Located in cytoplasm; microtubule cytoskeleton; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

NUAK1 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUAK1	NM_014840.3 link	c.513+62T>C		intron_variant	Intron 3 of 6	ENST00000261402.7	NP_055655.1	O60285-1A0A024RBL3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7 link	c.513+62T>C		intron_variant	Intron 3 of 6	1	NM_014840.3	ENSP00000261402.2		O60285-1
NUAK1	ENST00000548902.1 link	c.120+62T>C		intron_variant	Intron 1 of 4	4		ENSP00000448288.1		F8VSH4

Frequencies

GnomAD3 genomes

AF:

0.401

AC:

60865

AN:

151902

Hom.:

12099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.384

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.430

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.439

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.402

Gnomad OTH

AF:

0.386

GnomAD4 exome

AF:

0.409

AC:

560899

AN:

1372884

Hom.:

115268

AF XY:

0.408

AC XY:

275013

AN XY:

674458

show subpopulations

African (AFR)

AF:

0.373

AC:

11671

AN:

31274

American (AMR)

AF:

0.486

AC:

18458

AN:

37984

Ashkenazi Jewish (ASJ)

AF:

0.375

AC:

8574

AN:

22892

East Asian (EAS)

AF:

0.426

AC:

16367

AN:

38402

South Asian (SAS)

AF:

0.413

AC:

30855

AN:

74650

European-Finnish (FIN)

AF:

0.403

AC:

19600

AN:

48636

Middle Eastern (MID)

AF:

0.378

AC:

1643

AN:

4348

European-Non Finnish (NFE)

AF:

0.407

AC:

430717

AN:

1058278

Other (OTH)

AF:

0.408

AC:

23014

AN:

56420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

15654

31308

46961

62615

78269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13948

27896

41844

55792

69740

<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:

0.401

AC:

60921

AN:

152020

Hom.:

12118

Cov.:

AF XY:

0.404

AC XY:

29993

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.383

AC:

15893

AN:

41448

American (AMR)

AF:

0.431

AC:

6590

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1269

AN:

3472

East Asian (EAS)

AF:

0.439

AC:

2260

AN:

5150

South Asian (SAS)

AF:

0.424

AC:

2041

AN:

4814

European-Finnish (FIN)

AF:

0.414

AC:

4373

AN:

10562

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.402

AC:

27327

AN:

67968

Other (OTH)

AF:

0.385

AC:

813

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1958

3917

5875

7834

9792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

582

1164

1746

2328

2910

<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:

0.396

Hom.:

20072

Bravo

AF:

0.402

Asia WGS

AF:

0.449

AC:

1559

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.88

(source)

DANN

Benign

0.39

PhyloP100

-0.69

PromoterAI

-0.0059

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over