12-106086672-A-G

Variant names:

• chr12-106086672-A-G
• rs2251027
• NM_014840.3:c.513+62T>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.513+62T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,524,904 control chromosomes in the GnomAD database, including 127,386 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 0.40 (12118 hom., cov: 32)
  • Exomes 𝑓: 0.41 (115268 hom.)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.687
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.513+62T>C		intron_variant	Intron 3 of 6	ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7	c.513+62T>C		intron_variant	Intron 3 of 6	1	NM_014840.3	ENSP00000261402.2
NUAK1	ENST00000548902.1	c.120+62T>C		intron_variant	Intron 1 of 4	4		ENSP00000448288.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60865 AN: 151902 Hom.: 12099 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.409 AC: 560899 AN: 1372884 Hom.: 115268 AF XY: 0.408 AC XY: 275013 AN XY: 674458

African (AFR) AF: 0.373 AC: 11671 AN: 31274

American (AMR) AF: 0.486 AC: 18458 AN: 37984

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 8574 AN: 22892

East Asian (EAS) AF: 0.426 AC: 16367 AN: 38402

South Asian (SAS) AF: 0.413 AC: 30855 AN: 74650

European-Finnish (FIN) AF: 0.403 AC: 19600 AN: 48636

Middle Eastern (MID) AF: 0.378 AC: 1643 AN: 4348

European-Non Finnish (NFE) AF: 0.407 AC: 430717 AN: 1058278

Other (OTH) AF: 0.408 AC: 23014 AN: 56420

GnomAD4 genome AF: 0.401 AC: 60921 AN: 152020 Hom.: 12118 Cov.: 32 AF XY: 0.404 AC XY: 29993 AN XY: 74310

African (AFR) AF: 0.383 AC: 15893 AN: 41448

American (AMR) AF: 0.431 AC: 6590 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1269 AN: 3472

East Asian (EAS) AF: 0.439 AC: 2260 AN: 5150

South Asian (SAS) AF: 0.424 AC: 2041 AN: 4814

European-Finnish (FIN) AF: 0.414 AC: 4373 AN: 10562

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27327 AN: 67968

Other (OTH) AF: 0.385 AC: 813 AN: 2112

Alfa AF: 0.396 Hom.: 20072

Bravo AF: 0.402

Asia WGS AF: 0.449 AC: 1559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.88
DANN	Benign	0.39
PhyloP100		-0.69
PromoterAI		-0.0059	Neutral
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: rs2251027; hg19: chr12-106480450;