rs7133815

Positions:

• chr12-106082362-T-C
• chr12-106082362-T-G

Variant summary

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

The NM_014840.3(NUAK1):​c.579+1502A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,182 control chromosomes in the GnomAD database, including 3,588 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 0.20 (3588 hom., cov: 33)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.579+1502A>G		intron_variant		ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7	c.579+1502A>G		intron_variant		1	NM_014840.3	ENSP00000261402	P1
NUAK1	ENST00000548902.1	c.186+1502A>G		intron_variant		4		ENSP00000448288
NUAK1	ENST00000549704.1	c.-172+1502A>G		intron_variant		4		ENSP00000449990
NUAK1	ENST00000553094.1	c.-24+1502A>G		intron_variant		4		ENSP00000446873

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30322 AN: 152064 Hom.: 3581 Cov.: 33

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0633

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.200 AC: 30369 AN: 152182 Hom.: 3588 Cov.: 33 AF XY: 0.195 AC XY: 14483 AN XY: 74394

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0635

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.182

Alfa AF: 0.164 Hom.: 4620

Bravo AF: 0.207

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.095
DANN	Benign	0.49

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: rs7133815; hg19: chr12-106476140;