12-106068079-G-C

Variant names:

• chr12-106068079-G-C
• rs3741885
• NM_014840.3:c.833-124C>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.833-124C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 883,768 control chromosomes in the GnomAD database, including 8,689 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 0.11 (1472 hom., cov: 33)
  • Exomes 𝑓: 0.10 (7217 hom.)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 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.833-124C>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.833-124C>G		intron	N/A	ENSP00000261402.2
	NUAK1	ENST00000548902.1	TSL:4	c.440-124C>G		intron	N/A	ENSP00000448288.1
	NUAK1	ENST00000553094.1	TSL:4	c.-23-124C>G		intron	N/A	ENSP00000446873.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17118 AN: 152100 Hom.: 1474 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0877

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0525

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0719

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.100 AC: 73388 AN: 731550 Hom.: 7217 AF XY: 0.104 AC XY: 38347 AN XY: 367866

African (AFR) AF: 0.150 AC: 2710 AN: 18018

American (AMR) AF: 0.100 AC: 1910 AN: 19104

Ashkenazi Jewish (ASJ) AF: 0.0788 AC: 1206 AN: 15306

East Asian (EAS) AF: 0.506 AC: 16410 AN: 32432

South Asian (SAS) AF: 0.199 AC: 8812 AN: 44330

European-Finnish (FIN) AF: 0.0462 AC: 1386 AN: 30010

Middle Eastern (MID) AF: 0.136 AC: 540 AN: 3970

European-Non Finnish (NFE) AF: 0.0686 AC: 36567 AN: 532914

Other (OTH) AF: 0.108 AC: 3847 AN: 35466

GnomAD4 genome AF: 0.112 AC: 17111 AN: 152218 Hom.: 1472 Cov.: 33 AF XY: 0.116 AC XY: 8633 AN XY: 74428

African (AFR) AF: 0.142 AC: 5907 AN: 41520

American (AMR) AF: 0.101 AC: 1546 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0877 AC: 304 AN: 3468

East Asian (EAS) AF: 0.496 AC: 2559 AN: 5160

South Asian (SAS) AF: 0.197 AC: 949 AN: 4816

European-Finnish (FIN) AF: 0.0525 AC: 557 AN: 10612

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.0718 AC: 4886 AN: 68020

Other (OTH) AF: 0.128 AC: 270 AN: 2116

Alfa AF: 0.0824 Hom.: 84

Bravo AF: 0.118

Asia WGS AF: 0.296 AC: 1031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.77
DANN	Benign	0.68
PhyloP100		-0.089
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: rs3741885; hg19: chr12-106461857; COSMIC: COSV107217545;