12-106106630-T-C

Variant names:

• chr12-106106630-T-C
• rs1427785
• NM_014840.3:c.241-105A>G

Variant summary

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

The NM_014840.3(NUAK1):​c.241-105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,191,266 control chromosomes in the GnomAD database, including 126,045 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 0.47 (17021 hom., cov: 32)
  • Exomes 𝑓: 0.46 (109024 hom.)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55
• Publications: 7 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 (AFR) allele frequency at 95% confidence interval = 0.517 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.241-105A>G		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.241-105A>G		intron	N/A	ENSP00000261402.2

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71730 AN: 151904 Hom.: 16996 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.439

GnomAD4 exome AF: 0.456 AC: 473610 AN: 1039244 Hom.: 109024 AF XY: 0.455 AC XY: 236149 AN XY: 519006

African (AFR) AF: 0.515 AC: 12158 AN: 23588

American (AMR) AF: 0.464 AC: 13009 AN: 28008

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 7515 AN: 18476

East Asian (EAS) AF: 0.424 AC: 14824 AN: 34958

South Asian (SAS) AF: 0.467 AC: 25040 AN: 53586

European-Finnish (FIN) AF: 0.468 AC: 16021 AN: 34214

Middle Eastern (MID) AF: 0.425 AC: 1290 AN: 3036

European-Non Finnish (NFE) AF: 0.455 AC: 363545 AN: 798678

Other (OTH) AF: 0.452 AC: 20208 AN: 44700

GnomAD4 genome AF: 0.472 AC: 71803 AN: 152022 Hom.: 17021 Cov.: 32 AF XY: 0.473 AC XY: 35114 AN XY: 74302

African (AFR) AF: 0.522 AC: 21668 AN: 41474

American (AMR) AF: 0.454 AC: 6938 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1421 AN: 3472

East Asian (EAS) AF: 0.438 AC: 2267 AN: 5178

South Asian (SAS) AF: 0.470 AC: 2268 AN: 4822

European-Finnish (FIN) AF: 0.482 AC: 5077 AN: 10532

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30845 AN: 67952

Other (OTH) AF: 0.440 AC: 925 AN: 2100

Alfa AF: 0.463 Hom.: 12233

Bravo AF: 0.471

Asia WGS AF: 0.490 AC: 1699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.65
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1427785; hg19: chr12-106500408; COSMIC: COSV54605909; COSMIC: COSV54605909;