12-106106630-T-C

Position:

• chr12-106106630-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.241-105A>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.241-105A>G		intron_variant		1	NM_014840.3	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

Gnomad4 AFR exome AF: 0.515

Gnomad4 AMR exome AF: 0.464

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.424

Gnomad4 SAS exome AF: 0.467

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.455

Gnomad4 OTH exome AF: 0.452

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

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.440

Alfa AF: 0.463 Hom.: 9491

Bravo AF: 0.471

Asia WGS AF: 0.490 AC: 1699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs1427785; hg19: chr12-106500408; COSMIC: COSV54605909; COSMIC: COSV54605909;