rs11112868

Variant names:

• chr12-106104677-A-G
• rs11112868
• NM_014840.3:c.361+1728T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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]

ENSG00000257438 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.361+1728T>C		intron_variant	Intron 2 of 6	ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7	c.361+1728T>C		intron_variant	Intron 2 of 6	1	NM_014840.3	ENSP00000261402.2
ENSG00000257438	ENST00000548901.1	n.354+449A>G		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.733 AC: 30390 AN: 41462

American (AMR) AF: 0.502 AC: 7666 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1549 AN: 3472

East Asian (EAS) AF: 0.439 AC: 2264 AN: 5162

South Asian (SAS) AF: 0.478 AC: 2299 AN: 4812

European-Finnish (FIN) AF: 0.545 AC: 5747 AN: 10546

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33050 AN: 67970

Other (OTH) AF: 0.504 AC: 1063 AN: 2110

Alfa AF: 0.554 Hom.: 3390

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
PhyloP100		-0.86
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: rs11112868; hg19: chr12-106498455;