12-106066124-T-C

Variant names:

• chr12-106066124-T-C
• rs6539247
• NM_014840.3:c.*678A>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.*678A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,270 control chromosomes in the GnomAD database, including 26,817 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 0.59 (26768 hom., cov: 32)
  • Exomes 𝑓: 0.65 (49 hom.)
• Consequence: NUAK1 NM_014840.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.49
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUAK1	NM_014840.3	MANE Select	c.*678A>G		3_prime_UTR	Exon 7 of 7	NP_055655.1	O60285-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUAK1	ENST00000261402.7	TSL:1 MANE Select	c.*678A>G		3_prime_UTR	Exon 7 of 7	ENSP00000261402.2	O60285-1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89390 AN: 151954 Hom.: 26750 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.596

GnomAD4 exome AF: 0.646 AC: 128 AN: 198 Hom.: 49 Cov.: 0 AF XY: 0.692 AC XY: 83 AN XY: 120

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AF: 0.813 AC: 13 AN: 16

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.617 AC: 100 AN: 162

Other (OTH) AF: 0.700 AC: 7 AN: 10

GnomAD4 genome AF: 0.588 AC: 89455 AN: 152072 Hom.: 26768 Cov.: 32 AF XY: 0.589 AC XY: 43778 AN XY: 74316

African (AFR) AF: 0.570 AC: 23652 AN: 41472

American (AMR) AF: 0.595 AC: 9092 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1772 AN: 3470

East Asian (EAS) AF: 0.956 AC: 4945 AN: 5170

South Asian (SAS) AF: 0.658 AC: 3172 AN: 4822

European-Finnish (FIN) AF: 0.508 AC: 5362 AN: 10558

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39520 AN: 67976

Other (OTH) AF: 0.595 AC: 1255 AN: 2110

Alfa AF: 0.581 Hom.: 37211

Bravo AF: 0.597

Asia WGS AF: 0.770 AC: 2676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.010
DANN	Benign	0.57
PhyloP100		-3.5
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: rs6539247; hg19: chr12-106459902;