rs10492351

Positions:

• chr12-106115037-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014840.3(NUAK1):​c.241-8512T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 152,300 control chromosomes in the GnomAD database, including 367 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 0.063 (367 hom., cov: 32)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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 (NFE) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUAK1	NM_014840.3	c.241-8512T>C		intron_variant		ENST00000261402.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUAK1	ENST00000261402.7	c.241-8512T>C		intron_variant		1	NM_014840.3	P1

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 9639 AN: 152182 Hom.: 367 Cov.: 32

Gnomad AFR AF: 0.0291

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0636

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0241

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0747

Gnomad OTH AF: 0.0603

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0633 AC: 9645 AN: 152300 Hom.: 367 Cov.: 32 AF XY: 0.0646 AC XY: 4812 AN XY: 74468

Gnomad4 AFR AF: 0.0290

Gnomad4 AMR AF: 0.0636

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0241

Gnomad4 SAS AF: 0.0679

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0747

Gnomad4 OTH AF: 0.0597

Alfa AF: 0.0752 Hom.: 266

Bravo AF: 0.0594

Asia WGS AF: 0.0560 AC: 195 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	4.3
DANN	Benign	0.27

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: rs10492351; hg19: chr12-106508815;