rs2559602

Positions:

• chr12-106136383-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.240+2031G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 151,906 control chromosomes in the GnomAD database, including 16,215 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 0.44 (16215 hom., cov: 32)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.240+2031G>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.240+2031G>A		intron_variant		1	NM_014840.3	ENSP00000261402.2

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67032 AN: 151788 Hom.: 16217 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.441 AC: 67055 AN: 151906 Hom.: 16215 Cov.: 32 AF XY: 0.447 AC XY: 33212 AN XY: 74234

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.451

Alfa AF: 0.498 Hom.: 28805

Bravo AF: 0.423

Asia WGS AF: 0.494 AC: 1719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2559602; hg19: chr12-106530161;