rs2251027

chr12-106086672-A-Gchr12-106086672-A-T

Variant summary

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

The NM_014840.3(NUAK1):c.513+62T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,524,904 control chromosomes in the GnomAD database, including 127,386 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 0.40 (12118 hom., cov: 32)
  • Exomes 𝑓: 0.41 (115268 hom.)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUAK1	NM_014840.3	c.513+62T>C		intron_variant		ENST00000261402.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUAK1	ENST00000261402.7	c.513+62T>C		intron_variant		1	NM_014840.3	P1
NUAK1	ENST00000548902.1	c.120+62T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60865 AN: 151902 Hom.: 12099 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.409 AC: 560899 AN: 1372884 Hom.: 115268 AF XY: 0.408 AC XY: 275013 AN XY: 674458

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.486

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.426

Gnomad4 SAS exome AF: 0.413

Gnomad4 FIN exome AF: 0.403

Gnomad4 NFE exome AF: 0.407

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.401 AC: 60921 AN: 152020 Hom.: 12118 Cov.: 32 AF XY: 0.404 AC XY: 29993 AN XY: 74310

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.385

Alfa AF: 0.351 Hom.: 2199

Bravo AF: 0.402

Asia WGS AF: 0.449 AC: 1559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.88
Dann	Benign	0.39

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: rs2251027; hg19: chr12-106480450;