rs2434081

Variant names:

• chr12-106134676-C-T
• rs2434081
• NM_014840.3:c.240+3738G>A

Variant summary

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

The NM_014840.3(NUAK1):​c.240+3738G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,090 control chromosomes in the GnomAD database, including 33,626 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 0.66 (33626 hom., cov: 33)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501
• Publications: 4 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 (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014840.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUAK1	NM_014840.3	MANE Select	c.240+3738G>A		intron	N/A	NP_055655.1	O60285-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUAK1	ENST00000261402.7	TSL:1 MANE Select	c.240+3738G>A		intron	N/A	ENSP00000261402.2	O60285-1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99980 AN: 151974 Hom.: 33577 Cov.: 33

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.658 AC: 100086 AN: 152090 Hom.: 33626 Cov.: 33 AF XY: 0.661 AC XY: 49150 AN XY: 74332

African (AFR) AF: 0.778 AC: 32261 AN: 41478

American (AMR) AF: 0.668 AC: 10216 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2190 AN: 3472

East Asian (EAS) AF: 0.437 AC: 2262 AN: 5178

South Asian (SAS) AF: 0.578 AC: 2787 AN: 4820

European-Finnish (FIN) AF: 0.726 AC: 7676 AN: 10568

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40618 AN: 67956

Other (OTH) AF: 0.626 AC: 1322 AN: 2112

Alfa AF: 0.613 Hom.: 48249

Bravo AF: 0.656

Asia WGS AF: 0.546 AC: 1902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.66
PhyloP100		-0.50
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2434081;

hg19: chr12-106528454;