12-106123210-T-G

Variant names:

• chr12-106123210-T-G
• rs1215604
• NM_014840.3:c.240+15204A>C

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+15204A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 152,044 control chromosomes in the GnomAD database, including 13,080 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 0.38 (13080 hom., cov: 32)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.736
• Publications: 0 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.240+15204A>C		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+15204A>C		intron_variant	Intron 1 of 6	1	NM_014840.3	ENSP00000261402.2

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57296 AN: 151926 Hom.: 13080 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.377 AC: 57290 AN: 152044 Hom.: 13080 Cov.: 32 AF XY: 0.384 AC XY: 28519 AN XY: 74312

African (AFR) AF: 0.102 AC: 4252 AN: 41508

American (AMR) AF: 0.456 AC: 6955 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1695 AN: 3470

East Asian (EAS) AF: 0.461 AC: 2374 AN: 5154

South Asian (SAS) AF: 0.486 AC: 2337 AN: 4804

European-Finnish (FIN) AF: 0.522 AC: 5518 AN: 10568

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32670 AN: 67956

Other (OTH) AF: 0.406 AC: 858 AN: 2114

Alfa AF: 0.425 Hom.: 1945

Bravo AF: 0.353

Asia WGS AF: 0.456 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.2
DANN	Benign	0.57
PhyloP100		0.74
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: rs1215604; hg19: chr12-106516988;