chr12-106107672-C-G

Variant names:

• chr12-106107672-C-G
• rs4964439
• NM_014840.3:c.241-1147G>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.241-1147G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,138 control chromosomes in the GnomAD database, including 4,176 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 0.23 (4176 hom., cov: 32)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.241-1147G>C		intron_variant	Intron 1 of 6	ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7	c.241-1147G>C		intron_variant	Intron 1 of 6	1	NM_014840.3	ENSP00000261402.2

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35071 AN: 152020 Hom.: 4170 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0871

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.231 AC: 35102 AN: 152138 Hom.: 4176 Cov.: 32 AF XY: 0.230 AC XY: 17075 AN XY: 74372

African (AFR) AF: 0.246 AC: 10206 AN: 41480

American (AMR) AF: 0.249 AC: 3808 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 709 AN: 3468

East Asian (EAS) AF: 0.0867 AC: 450 AN: 5188

South Asian (SAS) AF: 0.186 AC: 896 AN: 4816

European-Finnish (FIN) AF: 0.258 AC: 2727 AN: 10586

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15603 AN: 67992

Other (OTH) AF: 0.200 AC: 421 AN: 2108

Alfa AF: 0.144 Hom.: 272

Bravo AF: 0.230

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.62
PhyloP100		0.34
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: rs4964439; hg19: chr12-106501450;