rs3741886

Positions:

• chr12-106073081-A-C
• chr12-106073081-A-G

Variant summary

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

The ENST00000261402.7(NUAK1):​c.580-238T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,202 control chromosomes in the GnomAD database, including 1,810 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 0.12 (1810 hom., cov: 32)
• Consequence: NUAK1 ENST00000261402.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.580-238T>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.580-238T>G		intron_variant		1	NM_014840.3	ENSP00000261402	P1
NUAK1	ENST00000548902.1	c.187-238T>G		intron_variant		4		ENSP00000448288
NUAK1	ENST00000549704.1	c.-171-238T>G		intron_variant		4		ENSP00000449990
NUAK1	ENST00000553094.1	c.-23-5126T>G		intron_variant		4		ENSP00000446873

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18986 AN: 152082 Hom.: 1808 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.0726

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.125 AC: 18995 AN: 152202 Hom.: 1810 Cov.: 32 AF XY: 0.128 AC XY: 9539 AN XY: 74438

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.0539

Gnomad4 NFE AF: 0.0726

Gnomad4 OTH AF: 0.139

Alfa AF: 0.0733 Hom.: 339

Bravo AF: 0.132

Asia WGS AF: 0.301 AC: 1046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.10
DANN	Benign	0.70

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: rs3741886; hg19: chr12-106466859; COSMIC: COSV54602218;