chr12-106083027-T-C

Variant names:

• chr12-106083027-T-C
• rs12146713
• NM_014840.3:c.579+837A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_014840.3(NUAK1):​c.579+837A>G variant causes a intron change. The variant allele was found at a frequency of 0.055 in 152,182 control chromosomes in the GnomAD database, including 324 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 0.055 (324 hom., cov: 32)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.86
• Publications: 14 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.579+837A>G		intron_variant	Intron 4 of 6	ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7	c.579+837A>G		intron_variant	Intron 4 of 6	1	NM_014840.3	ENSP00000261402.2
NUAK1	ENST00000548902.1	c.186+837A>G		intron_variant	Intron 2 of 4	4		ENSP00000448288.1
NUAK1	ENST00000553094.1	c.-24+837A>G		intron_variant	Intron 1 of 1	4		ENSP00000446873.1
NUAK1	ENST00000549704.1	c.-172+837A>G		intron_variant	Intron 1 of 3	4		ENSP00000449990.1

Frequencies

GnomAD3 genomes AF: 0.0550 AC: 8366 AN: 152064 Hom.: 324 Cov.: 32

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.0444

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0604

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0866

Gnomad OTH AF: 0.0551

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

GnomAD4 genome AF: 0.0550 AC: 8366 AN: 152182 Hom.: 324 Cov.: 32 AF XY: 0.0524 AC XY: 3894 AN XY: 74384

African (AFR) AF: 0.0156 AC: 646 AN: 41542

American (AMR) AF: 0.0444 AC: 678 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0604 AC: 291 AN: 4814

European-Finnish (FIN) AF: 0.0431 AC: 456 AN: 10586

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0867 AC: 5893 AN: 68002

Other (OTH) AF: 0.0545 AC: 115 AN: 2110

Alfa AF: 0.0743 Hom.: 977

Bravo AF: 0.0535

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Benign	0.72
PhyloP100		4.9
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: rs12146713; hg19: chr12-106476805;