12-106078423-C-T

Variant names:

• chr12-106078423-C-T
• rs17038085
• NM_014840.3:c.579+5441G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014840.3(NUAK1):​c.579+5441G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,190 control chromosomes in the GnomAD database, including 2,520 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 0.16 (2520 hom., cov: 33)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.579+5441G>A		intron_variant	Intron 4 of 6	ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7	c.579+5441G>A		intron_variant	Intron 4 of 6	1	NM_014840.3	ENSP00000261402.2
NUAK1	ENST00000548902.1	c.186+5441G>A		intron_variant	Intron 2 of 4	4		ENSP00000448288.1
NUAK1	ENST00000553094.1	c.-24+5441G>A		intron_variant	Intron 1 of 1	4		ENSP00000446873.1
NUAK1	ENST00000549704.1	c.-172+5441G>A		intron_variant	Intron 1 of 3	4		ENSP00000449990.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24527 AN: 152072 Hom.: 2517 Cov.: 33

Gnomad AFR AF: 0.0404

Gnomad AMI AF: 0.0419

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.161 AC: 24549 AN: 152190 Hom.: 2520 Cov.: 33 AF XY: 0.165 AC XY: 12281 AN XY: 74384

African (AFR) AF: 0.0402 AC: 1672 AN: 41554

American (AMR) AF: 0.178 AC: 2723 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3468

East Asian (EAS) AF: 0.395 AC: 2043 AN: 5176

South Asian (SAS) AF: 0.247 AC: 1191 AN: 4820

European-Finnish (FIN) AF: 0.199 AC: 2103 AN: 10576

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13707 AN: 67992

Other (OTH) AF: 0.185 AC: 391 AN: 2112

Alfa AF: 0.179 Hom.: 433

Bravo AF: 0.155

Asia WGS AF: 0.291 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.014
DANN	Benign	0.54
PhyloP100		-2.1
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: rs17038085; hg19: chr12-106472201;