rs1215597

Positions:

• chr12-106138294-C-A

Variant summary

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

The NM_014840.3(NUAK1):​c.240+120G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,356,388 control chromosomes in the GnomAD database, including 150,443 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 0.39 (13297 hom., cov: 32)
  • Exomes 𝑓: 0.47 (137146 hom.)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.256

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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.240+120G>T		intron_variant		ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7	c.240+120G>T		intron_variant		1	NM_014840.3	ENSP00000261402	P1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59754 AN: 151808 Hom.: 13298 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.402

GnomAD4 exome AF: 0.473 AC: 570229 AN: 1204462 Hom.: 137146 AF XY: 0.475 AC XY: 279611 AN XY: 588548

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.510

Gnomad4 ASJ exome AF: 0.440

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.516

Gnomad4 FIN exome AF: 0.512

Gnomad4 NFE exome AF: 0.484

Gnomad4 OTH exome AF: 0.458

GnomAD4 genome AF: 0.393 AC: 59768 AN: 151926 Hom.: 13297 Cov.: 32 AF XY: 0.398 AC XY: 29552 AN XY: 74210

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.400

Alfa AF: 0.463 Hom.: 22170

Bravo AF: 0.379

Asia WGS AF: 0.444 AC: 1546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.7
DANN	Benign	0.88

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: rs1215597; hg19: chr12-106532072; COSMIC: COSV54607274;