rs10861556

Positions:

• chr12-106109867-A-C
• chr12-106109867-A-T

Variant summary

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

The NM_014840.3(NUAK1):​c.241-3342T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,050 control chromosomes in the GnomAD database, including 7,253 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 (7253 hom., cov: 32)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.590

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.241-3342T>G		intron_variant		ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7	c.241-3342T>G		intron_variant		1	NM_014840.3	ENSP00000261402	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43269 AN: 151934 Hom.: 7242 Cov.: 32

Gnomad AFR AF: 0.0906

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.285 AC: 43303 AN: 152050 Hom.: 7253 Cov.: 32 AF XY: 0.289 AC XY: 21470 AN XY: 74322

Gnomad4 AFR AF: 0.0906

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.296

Alfa AF: 0.340 Hom.: 13486

Bravo AF: 0.270

Asia WGS AF: 0.349 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
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: rs10861556; hg19: chr12-106503645;