12-106098517-T-C

Position:

• chr12-106098517-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014840.3(NUAK1):​c.361+7888A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 152,024 control chromosomes in the GnomAD database, including 29,914 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 0.60 (29914 hom., cov: 31)
• Consequence: NUAK1 NM_014840.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.361+7888A>G		intron_variant		ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7	c.361+7888A>G		intron_variant		1	NM_014840.3	ENSP00000261402	P1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90874 AN: 151906 Hom.: 29841 Cov.: 31

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.599 AC: 91016 AN: 152024 Hom.: 29914 Cov.: 31 AF XY: 0.596 AC XY: 44274 AN XY: 74292

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.539

Alfa AF: 0.549 Hom.: 3864

Bravo AF: 0.611

Asia WGS AF: 0.520 AC: 1807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.4
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs967872; hg19: chr12-106492295;