chr12-106066896-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_014840.3(NUAK1):c.1892G>A(p.Arg631Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,614,108 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00058 ( 5 hom., cov: 33)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
NUAK1
NM_014840.3 missense
NM_014840.3 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 3.33
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0065428913).
BS2
?
High Homozygotes in GnomAd at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NUAK1 | NM_014840.3 | c.1892G>A | p.Arg631Gln | missense_variant | 7/7 | ENST00000261402.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NUAK1 | ENST00000261402.7 | c.1892G>A | p.Arg631Gln | missense_variant | 7/7 | 1 | NM_014840.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000578 AC: 88AN: 152246Hom.: 5 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251352Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135866
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GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461862Hom.: 0 Cov.: 30 AF XY: 0.0000481 AC XY: 35AN XY: 727226
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GnomAD4 genome ? AF: 0.000578 AC: 88AN: 152246Hom.: 5 Cov.: 33 AF XY: 0.000578 AC XY: 43AN XY: 74382
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 12, 2023 | The c.1892G>A (p.R631Q) alteration is located in exon 7 (coding exon 7) of the NUAK1 gene. This alteration results from a G to A substitution at nucleotide position 1892, causing the arginine (R) at amino acid position 631 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of loop (P = 0.0013);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at