rs12297025

chr12-106112469-T-A

Variant summary

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

The NM_014840.3(NUAK1):c.241-5944A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,008 control chromosomes in the GnomAD database, including 11,313 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 0.28 (11313 hom., cov: 31)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUAK1	NM_014840.3	c.241-5944A>T		intron_variant		ENST00000261402.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUAK1	ENST00000261402.7	c.241-5944A>T		intron_variant		1	NM_014840.3	P1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43140 AN: 151890 Hom.: 11273 Cov.: 31

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.284 AC: 43243 AN: 152008 Hom.: 11313 Cov.: 31 AF XY: 0.279 AC XY: 20706 AN XY: 74308

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.218

Alfa AF: 0.221 Hom.: 904

Bravo AF: 0.304

Asia WGS AF: 0.178 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.33
Dann	Benign	0.51

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: rs12297025; hg19: chr12-106506247;