Variant 12-106067291-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014840.3(NUAK1):c.1497C>A(p.Ser499Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000325 in 1,613,974 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00034 ( 1 hom. )

Consequence

NUAK1
NM_014840.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.357

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06878206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUAK1	NM_014840.3 linkuse as main transcript	c.1497C>A	p.Ser499Arg	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.1497C>A	p.Ser499Arg	missense_variant	7/7	1	NM_014840.3	P1	O60285-1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000143

AC:

AN:

251320

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000341

AC:

498

AN:

1461812

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

244

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000431

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.000171

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000237

Hom.:

Bravo

AF:

0.000136

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2023

The c.1497C>A (p.S499R) alteration is located in exon 7 (coding exon 7) of the NUAK1 gene. This alteration results from a C to A substitution at nucleotide position 1497, causing the serine (S) at amino acid position 499 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.50

Cadd

Benign

5.5

Dann

Benign

0.95

DEOGEN2

Benign

0.12

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.68

M_CAP

Benign

0.052

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.82

REVEL

Benign

0.10

Sift

Benign

0.030

Sift4G

Benign

0.47

Polyphen

0.024

Vest4

0.080

MutPred

0.32

Loss of sheet (P = 7e-04);

MVP

0.69

MPC

0.50

ClinPred

0.028

GERP RS

-0.27

Varity_R

0.13

gMVP

0.12

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over