rs12582194

Positions:

• chr12-106088155-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014840.3(NUAK1):​c.362-1270G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,116 control chromosomes in the GnomAD database, including 6,613 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 0.29 (6613 hom., cov: 33)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.362-1270G>A		intron_variant		ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7	c.362-1270G>A		intron_variant		1	NM_014840.3	ENSP00000261402.2

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43591 AN: 151996 Hom.: 6601 Cov.: 33

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.298

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.287 AC: 43626 AN: 152116 Hom.: 6613 Cov.: 33 AF XY: 0.286 AC XY: 21265 AN XY: 74366

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.295

Alfa AF: 0.255 Hom.: 808

Bravo AF: 0.296

Asia WGS AF: 0.337 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs12582194; hg19: chr12-106481933;