NM_014840.3:c.240+15315A>G

Variant names:

• chr12-106123099-T-C
• rs1215603
• NM_014840.3:c.240+15315A>G

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+15315A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,104 control chromosomes in the GnomAD database, including 25,689 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 0.58 (25689 hom., cov: 33)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.240+15315A>G		intron_variant	Intron 1 of 6	ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7	c.240+15315A>G		intron_variant	Intron 1 of 6	1	NM_014840.3	ENSP00000261402.2

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88097 AN: 151986 Hom.: 25670 Cov.: 33

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.580 AC: 88157 AN: 152104 Hom.: 25689 Cov.: 33 AF XY: 0.579 AC XY: 43011 AN XY: 74346

African (AFR) AF: 0.629 AC: 26097 AN: 41492

American (AMR) AF: 0.568 AC: 8674 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1968 AN: 3470

East Asian (EAS) AF: 0.529 AC: 2733 AN: 5170

South Asian (SAS) AF: 0.518 AC: 2495 AN: 4816

European-Finnish (FIN) AF: 0.560 AC: 5928 AN: 10580

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38326 AN: 67978

Other (OTH) AF: 0.573 AC: 1208 AN: 2110

Alfa AF: 0.572 Hom.: 5258

Bravo AF: 0.579

Asia WGS AF: 0.526 AC: 1831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.22
PhyloP100		-0.95
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

Other links and lift over

dbSNP: rs1215603; hg19: chr12-106516877;