NM_014840.3:c.241-8512T>C

Variant names:

• chr12-106115037-A-G
• rs10492351
• NM_014840.3:c.241-8512T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.073 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUAK1	NM_014840.3	MANE Select	c.241-8512T>C		intron	N/A	NP_055655.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUAK1	ENST00000261402.7	TSL:1 MANE Select	c.241-8512T>C		intron	N/A	ENSP00000261402.2

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

African (AFR) AF: 0.0290 AC: 1206 AN: 41576

American (AMR) AF: 0.0636 AC: 973 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 439 AN: 3472

East Asian (EAS) AF: 0.0241 AC: 125 AN: 5184

South Asian (SAS) AF: 0.0679 AC: 328 AN: 4828

European-Finnish (FIN) AF: 0.115 AC: 1217 AN: 10598

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0747 AC: 5080 AN: 68028

Other (OTH) AF: 0.0597 AC: 126 AN: 2110

Alfa AF: 0.0756 Hom.: 294

Bravo AF: 0.0594

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.27
PhyloP100		0.26
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: rs10492351; hg19: chr12-106508815;