rs3741883

Variant names:

• chr12-106067160-G-C
• rs3741883
• NM_014840.3:c.1628C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-106067160-G-C
• chr12-106067160-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3186 hom., cov: 32)
  • Exomes 𝑓: 0.23 (40260 hom.)
• Consequence: NUAK1 NM_014840.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.61
• Publications: 26 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.1628C>G	p.Pro543Arg	missense_variant	Exon 7 of 7	ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7	c.1628C>G	p.Pro543Arg	missense_variant	Exon 7 of 7	1	NM_014840.3	ENSP00000261402.2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28397 AN: 152004 Hom.: 3185 Cov.: 32

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

GnomAD2 exomes AF: 0.228 AC: 57238 AN: 251306 AF XY: 0.232

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 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.: 36 AF XY: 0.232 AC XY: 168989 AN XY: 727240

African (AFR) AF: 0.0645 AC: 2158 AN: 33480

American (AMR) AF: 0.203 AC: 9094 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 6589 AN: 26136

East Asian (EAS) AF: 0.405 AC: 16080 AN: 39698

South Asian (SAS) AF: 0.262 AC: 22612 AN: 86254

European-Finnish (FIN) AF: 0.200 AC: 10682 AN: 53420

Middle Eastern (MID) AF: 0.242 AC: 1397 AN: 5768

European-Non Finnish (NFE) AF: 0.229 AC: 254913 AN: 1111986

Other (OTH) AF: 0.233 AC: 14072 AN: 60394

GnomAD4 genome AF: 0.187 AC: 28416 AN: 152122 Hom.: 3186 Cov.: 32 AF XY: 0.190 AC XY: 14105 AN XY: 74364

African (AFR) AF: 0.0691 AC: 2870 AN: 41518

American (AMR) AF: 0.202 AC: 3087 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 881 AN: 3468

East Asian (EAS) AF: 0.412 AC: 2120 AN: 5140

South Asian (SAS) AF: 0.271 AC: 1305 AN: 4808

European-Finnish (FIN) AF: 0.207 AC: 2197 AN: 10590

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15373 AN: 67992

Other (OTH) AF: 0.220 AC: 464 AN: 2110

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	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.094	T
Eigen	Benign	0.075
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.6
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.18
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.082	T
Polyphen		0.93	P
Vest4		0.093
MPC		0.76
ClinPred		0.034	T
GERP RS		5.5
Varity_R		0.070
gMVP		0.70
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3741883; hg19: chr12-106460938; COSMIC: COSV54601561; COSMIC: COSV54601561;