12-106068079-G-C

Position:

• chr12-106068079-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.833-124C>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.833-124C>G		intron_variant		1	NM_014840.3	ENSP00000261402.2
NUAK1	ENST00000548902.1	c.440-124C>G		intron_variant		4		ENSP00000448288.1
NUAK1	ENST00000553094.1	c.-23-124C>G		intron_variant		4		ENSP00000446873.1
NUAK1	ENST00000549704.1	c.83-124C>G		intron_variant		4		ENSP00000449990.1

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

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.0788

Gnomad4 EAS exome AF: 0.506

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.0462

Gnomad4 NFE exome AF: 0.0686

Gnomad4 OTH exome AF: 0.108

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

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0877

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.0525

Gnomad4 NFE AF: 0.0718

Gnomad4 OTH AF: 0.128

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.77
DANN	Benign	0.68

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: rs3741885; hg19: chr12-106461857;