12-106112469-T-A

Variant names:

• chr12-106112469-T-A
• rs12297025
• NM_014840.3:c.241-5944A>T

Variant summary

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

The NM_014840.3(NUAK1):​c.241-5944A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,008 control chromosomes in the GnomAD database, including 11,313 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 0.28 (11313 hom., cov: 31)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUAK1	NM_014840.3	MANE Select	c.241-5944A>T		intron	N/A	NP_055655.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUAK1	ENST00000261402.7	TSL:1 MANE Select	c.241-5944A>T		intron	N/A	ENSP00000261402.2

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43140 AN: 151890 Hom.: 11273 Cov.: 31

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.284 AC: 43243 AN: 152008 Hom.: 11313 Cov.: 31 AF XY: 0.279 AC XY: 20706 AN XY: 74308

African (AFR) AF: 0.702 AC: 29091 AN: 41446

American (AMR) AF: 0.161 AC: 2454 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3468

East Asian (EAS) AF: 0.121 AC: 624 AN: 5144

South Asian (SAS) AF: 0.121 AC: 579 AN: 4794

European-Finnish (FIN) AF: 0.161 AC: 1708 AN: 10596

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7557 AN: 67970

Other (OTH) AF: 0.218 AC: 460 AN: 2110

Alfa AF: 0.221 Hom.: 904

Bravo AF: 0.304

Asia WGS AF: 0.178 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.33
DANN	Benign	0.51
PhyloP100		-0.42
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: rs12297025; hg19: chr12-106506247;