12-106084779-G-A

Variant names:

• chr12-106084779-G-A
• rs11112856
• NM_014840.3:c.514-850C>T

Variant summary

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

The NM_014840.3(NUAK1):​c.514-850C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 144,054 control chromosomes in the GnomAD database, including 931 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 0.10 (931 hom., cov: 32)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUAK1	NM_014840.3	MANE Select	c.514-850C>T		intron	N/A	NP_055655.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUAK1	ENST00000261402.7	TSL:1 MANE Select	c.514-850C>T		intron	N/A	ENSP00000261402.2
	NUAK1	ENST00000548902.1	TSL:4	c.121-850C>T		intron	N/A	ENSP00000448288.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 14637 AN: 143914 Hom.: 932 Cov.: 32

Gnomad AFR AF: 0.0301

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.000484

Gnomad SAS AF: 0.0676

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.102 AC: 14635 AN: 144054 Hom.: 931 Cov.: 32 AF XY: 0.0985 AC XY: 6903 AN XY: 70110

African (AFR) AF: 0.0301 AC: 1205 AN: 40046

American (AMR) AF: 0.102 AC: 1485 AN: 14624

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 373 AN: 3346

East Asian (EAS) AF: 0.000484 AC: 2 AN: 4128

South Asian (SAS) AF: 0.0676 AC: 270 AN: 3992

European-Finnish (FIN) AF: 0.125 AC: 1157 AN: 9224

Middle Eastern (MID) AF: 0.144 AC: 41 AN: 284

European-Non Finnish (NFE) AF: 0.148 AC: 9696 AN: 65480

Other (OTH) AF: 0.115 AC: 236 AN: 2058

Alfa AF: 0.122 Hom.: 661

Bravo AF: 0.0936

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.8
DANN	Benign	0.79
PhyloP100		-0.55
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: rs11112856; hg19: chr12-106478557; COSMIC: COSV54608041; COSMIC: COSV54608041;