chr12-106066124-T-C

Position:

• chr12-106066124-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.*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

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.*678A>G		3_prime_UTR_variant	7/7	ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402	c.*678A>G		3_prime_UTR_variant	7/7	1	NM_014840.3	ENSP00000261402.2

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

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.813

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.617

Gnomad4 OTH exome AF: 0.700

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

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.595

Alfa AF: 0.571 Hom.: 24346

Bravo AF: 0.597

Asia WGS AF: 0.770 AC: 2676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.010
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs6539247; hg19: chr12-106459902;