12-106090734-C-T

Position:

• chr12-106090734-C-T

Variant summary

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

The NM_014840.3(NUAK1):​c.362-3849G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.947 in 152,200 control chromosomes in the GnomAD database, including 68,394 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 0.95 (68394 hom., cov: 31)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUAK1	NM_014840.3	c.362-3849G>A		intron_variant		ENST00000261402.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUAK1	ENST00000261402.7	c.362-3849G>A		intron_variant		1	NM_014840.3	P1

Frequencies

GnomAD3 genomes AF: 0.947 AC: 144035 AN: 152082 Hom.: 68325 Cov.: 31

Gnomad AFR AF: 0.987

Gnomad AMI AF: 0.936

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.815

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.937

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

GnomAD4 genome AF: 0.947 AC: 144166 AN: 152200 Hom.: 68394 Cov.: 31 AF XY: 0.949 AC XY: 70631 AN XY: 74410

Gnomad4 AFR AF: 0.987

Gnomad4 AMR AF: 0.949

Gnomad4 ASJ AF: 0.871

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.944

Gnomad4 FIN AF: 0.973

Gnomad4 NFE AF: 0.920

Gnomad4 OTH AF: 0.938

Alfa AF: 0.928 Hom.: 32893

Bravo AF: 0.947

Asia WGS AF: 0.978 AC: 3401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.52

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: rs1366041; hg19: chr12-106484512;