12-106099369-C-G

Variant names:

• chr12-106099369-C-G
• rs1560000
• NM_014840.3:c.361+7036G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014840.3(NUAK1):​c.361+7036G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,044 control chromosomes in the GnomAD database, including 11,304 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 0.37 (11304 hom., cov: 32)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.361+7036G>C		intron_variant	Intron 2 of 6	ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7	c.361+7036G>C		intron_variant	Intron 2 of 6	1	NM_014840.3	ENSP00000261402.2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56103 AN: 151926 Hom.: 11291 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.369 AC: 56151 AN: 152044 Hom.: 11304 Cov.: 32 AF XY: 0.374 AC XY: 27757 AN XY: 74290

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.380

Alfa AF: 0.274 Hom.: 744

Bravo AF: 0.356

Asia WGS AF: 0.437 AC: 1516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs1560000; hg19: chr12-106493147;