chr12-106083411-C-G

Variant names:

• chr12-106083411-C-G
• rs1560757
• NM_014840.3:c.579+453G>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.579+453G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,130 control chromosomes in the GnomAD database, including 3,340 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 0.20 (3340 hom., cov: 33)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014840.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUAK1	NM_014840.3	MANE Select	c.579+453G>C		intron	N/A	NP_055655.1	O60285-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUAK1	ENST00000261402.7	TSL:1 MANE Select	c.579+453G>C		intron	N/A	ENSP00000261402.2	O60285-1
	NUAK1	ENST00000548902.1	TSL:4	c.186+453G>C		intron	N/A	ENSP00000448288.1	F8VSH4
	NUAK1	ENST00000553094.1	TSL:4	c.-24+453G>C		intron	N/A	ENSP00000446873.1	F8VZ96

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30999 AN: 152014 Hom.: 3335 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.204 AC: 31026 AN: 152130 Hom.: 3340 Cov.: 33 AF XY: 0.207 AC XY: 15400 AN XY: 74366

African (AFR) AF: 0.139 AC: 5781 AN: 41510

American (AMR) AF: 0.202 AC: 3092 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3472

East Asian (EAS) AF: 0.399 AC: 2066 AN: 5174

South Asian (SAS) AF: 0.262 AC: 1262 AN: 4814

European-Finnish (FIN) AF: 0.235 AC: 2489 AN: 10582

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 14998 AN: 67978

Other (OTH) AF: 0.213 AC: 451 AN: 2114

Alfa AF: 0.0761 Hom.: 104

Bravo AF: 0.198

Asia WGS AF: 0.308 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.55
PhyloP100		-1.2
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: rs1560757; hg19: chr12-106477189;