chr12-106086853-T-TG

Variant names:

• chr12-106086853-T-TG
• rs34594928
• NM_014840.3:c.393dupC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014840.3(NUAK1):​c.393dupC​(p.Met132HisfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUAK1 NM_014840.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.02
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUAK1	NM_014840.3	c.393dupC	p.Met132HisfsTer15	frameshift_variant	Exon 3 of 7	ENST00000261402.7	NP_055655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUAK1	ENST00000261402.7	c.393dupC	p.Met132HisfsTer15	frameshift_variant	Exon 3 of 7	1	NM_014840.3	ENSP00000261402.2
NUAK1	ENST00000548902.1	c.-1dupC		start_retained_variant	Exon 1 of 5	4		ENSP00000448288.1
NUAK1	ENST00000548902.1	c.-1dupC		5_prime_UTR_variant	Exon 1 of 5	4		ENSP00000448288.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0

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: rs34594928; hg19: chr12-106480631;