rs11112868

chr12-106104677-A-G

Variant summary

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

The NM_014840.3(NUAK1):c.361+1728T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,022 control chromosomes in the GnomAD database, including 24,371 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 0.56 (24371 hom., cov: 32)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUAK1	NM_014840.3	c.361+1728T>C		intron_variant		ENST00000261402.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUAK1	ENST00000261402.7	c.361+1728T>C		intron_variant		1	NM_014840.3	P1
	ENST00000548901.1	n.354+449A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84375 AN: 151904 Hom.: 24325 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.556 AC: 84482 AN: 152022 Hom.: 24371 Cov.: 32 AF XY: 0.555 AC XY: 41192 AN XY: 74270

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.545

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.504

Alfa AF: 0.548 Hom.: 3184

Bravo AF: 0.559

Asia WGS AF: 0.511 AC: 1773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.36
Dann	Benign	0.45

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: rs11112868; hg19: chr12-106498455;