NM_014840.3:c.241-5031A>C

Variant names:

• chr12-106111556-T-G
• rs11112872
• NM_014840.3:c.241-5031A>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.241-5031A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,806 control chromosomes in the GnomAD database, including 7,434 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 0.29 (7434 hom., cov: 31)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.368 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUAK1	NM_014840.3	MANE Select	c.241-5031A>C		intron	N/A	NP_055655.1	O60285-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUAK1	ENST00000261402.7	TSL:1 MANE Select	c.241-5031A>C		intron	N/A	ENSP00000261402.2	O60285-1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43760 AN: 151688 Hom.: 7423 Cov.: 31

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.288 AC: 43795 AN: 151806 Hom.: 7434 Cov.: 31 AF XY: 0.293 AC XY: 21728 AN XY: 74176

African (AFR) AF: 0.0914 AC: 3788 AN: 41446

American (AMR) AF: 0.340 AC: 5179 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 992 AN: 3462

East Asian (EAS) AF: 0.340 AC: 1740 AN: 5114

South Asian (SAS) AF: 0.376 AC: 1807 AN: 4802

European-Finnish (FIN) AF: 0.400 AC: 4208 AN: 10532

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.372 AC: 25227 AN: 67898

Other (OTH) AF: 0.301 AC: 636 AN: 2110

Alfa AF: 0.317 Hom.: 1117

Bravo AF: 0.273

Asia WGS AF: 0.358 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.76
PhyloP100		0.42
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: rs11112872; hg19: chr12-106505334;