chr12-106075393-C-T

Position:

• chr12-106075393-C-T

Variant summary

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

The ENST00000261402.7(NUAK1):​c.580-2550G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 151,752 control chromosomes in the GnomAD database, including 42,565 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 0.74 (42565 hom., cov: 30)
• Consequence: NUAK1 ENST00000261402.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.580-2550G>A		intron_variant		ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7	c.580-2550G>A		intron_variant		1	NM_014840.3	ENSP00000261402	P1
NUAK1	ENST00000548902.1	c.187-2550G>A		intron_variant		4		ENSP00000448288
NUAK1	ENST00000549704.1	c.-171-2550G>A		intron_variant		4		ENSP00000449990
NUAK1	ENST00000553094.1	c.-23-7438G>A		intron_variant		4		ENSP00000446873

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111800 AN: 151632 Hom.: 42503 Cov.: 30

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.738 AC: 111924 AN: 151752 Hom.: 42565 Cov.: 30 AF XY: 0.736 AC XY: 54575 AN XY: 74106

Gnomad4 AFR AF: 0.923

Gnomad4 AMR AF: 0.698

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.976

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.718

Alfa AF: 0.704 Hom.: 7120

Bravo AF: 0.754

Asia WGS AF: 0.814 AC: 2830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.036
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs934085; hg19: chr12-106469171;