Variant rs3741883 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014840.3(NUAK1):c.1628C>G(p.Pro543Arg) variant causes a missense change. The variant allele was found at a frequency of 0.227 in 1,613,982 control chromosomes in the GnomAD database, including 43,446 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3186 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40260 hom. )

Consequence

NUAK1
NM_014840.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.61

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024906397).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUAK1	NM_014840.3 linkuse as main transcript	c.1628C>G	p.Pro543Arg	missense_variant	7/7	ENST00000261402.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUAK1	ENST00000261402.7 linkuse as main transcript	c.1628C>G	p.Pro543Arg	missense_variant	7/7	1	NM_014840.3	P1	O60285-1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28397

AN:

152004

Hom.:

3185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0693

Gnomad AMI

AF:

0.0617

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.412

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.218

GnomAD3 exomes

AF:

0.228

AC:

57238

AN:

251306

Hom.:

7172

AF XY:

0.232

AC XY:

31556

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.0654

Gnomad AMR exome

AF:

0.201

Gnomad ASJ exome

AF:

0.249

Gnomad EAS exome

AF:

0.420

Gnomad SAS exome

AF:

0.262

Gnomad FIN exome

AF:

0.201

Gnomad NFE exome

AF:

0.222

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.231

AC:

337597

AN:

1461860

Hom.:

40260

Cov.:

AF XY:

0.232

AC XY:

168989

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0645

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.252

Gnomad4 EAS exome

AF:

0.405

Gnomad4 SAS exome

AF:

0.262

Gnomad4 FIN exome

AF:

0.200

Gnomad4 NFE exome

AF:

0.229

Gnomad4 OTH exome

AF:

0.233

GnomAD4 genome

AF:

0.187

AC:

28416

AN:

152122

Hom.:

3186

Cov.:

AF XY:

0.190

AC XY:

14105

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0691

Gnomad4 AMR

AF:

0.202

Gnomad4 ASJ

AF:

0.254

Gnomad4 EAS

AF:

0.412

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.207

Gnomad4 NFE

AF:

0.226

Gnomad4 OTH

AF:

0.220

Alfa

AF:

0.215

Hom.:

2473

Bravo

AF:

0.183

TwinsUK

AF:

0.232

AC:

861

ALSPAC

AF:

0.229

AC:

884

ESP6500AA

AF:

0.0695

AC:

306

ESP6500EA

AF:

0.228

AC:

1961

ExAC

AF:

0.224

AC:

27232

Asia WGS

AF:

0.304

AC:

1056

AN:

3478

EpiCase

AF:

0.233

EpiControl

AF:

0.227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.094

Eigen

Benign

0.075

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.029

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.11

REVEL

Benign

0.18

Sift

Uncertain

0.0040

Sift4G

Benign

0.082

Polyphen

0.93

Vest4

0.093

MPC

0.76

ClinPred

0.034

GERP RS

5.5

Varity_R

0.070

gMVP

0.70

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