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GeneBe

12-106067435-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_014840.3(NUAK1):c.1353G>A(p.Pro451=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00445 in 1,614,144 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 46 hom., cov: 33)
Exomes 𝑓: 0.0033 ( 43 hom. )

Consequence

NUAK1
NM_014840.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -8.06
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-106067435-C-T is Benign according to our data. Variant chr12-106067435-C-T is described in ClinVar as [Benign]. Clinvar id is 779952.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-8.06 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.015 (2290/152252) while in subpopulation AFR AF= 0.0443 (1842/41536). AF 95% confidence interval is 0.0427. There are 46 homozygotes in gnomad4. There are 1084 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 45 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NUAK1NM_014840.3 linkuse as main transcriptc.1353G>A p.Pro451= synonymous_variant 7/7 ENST00000261402.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NUAK1ENST00000261402.7 linkuse as main transcriptc.1353G>A p.Pro451= synonymous_variant 7/71 NM_014840.3 P1O60285-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0150
AC:
2282
AN:
152134
Hom.:
45
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0443
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0108
Gnomad ASJ
AF:
0.0130
Gnomad EAS
AF:
0.0245
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.00115
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.00754
AC:
1894
AN:
251340
Hom.:
26
AF XY:
0.00637
AC XY:
865
AN XY:
135838
show subpopulations
Gnomad AFR exome
AF:
0.0452
Gnomad AMR exome
AF:
0.00639
Gnomad ASJ exome
AF:
0.0116
Gnomad EAS exome
AF:
0.0301
Gnomad SAS exome
AF:
0.00242
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00138
Gnomad OTH exome
AF:
0.00587
GnomAD4 exome
AF:
0.00334
AC:
4886
AN:
1461892
Hom.:
43
Cov.:
33
AF XY:
0.00325
AC XY:
2365
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0449
Gnomad4 AMR exome
AF:
0.00686
Gnomad4 ASJ exome
AF:
0.0108
Gnomad4 EAS exome
AF:
0.0242
Gnomad4 SAS exome
AF:
0.00214
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00110
Gnomad4 OTH exome
AF:
0.00666
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0150
AC:
2290
AN:
152252
Hom.:
46
Cov.:
33
AF XY:
0.0146
AC XY:
1084
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0443
Gnomad4 AMR
AF:
0.0108
Gnomad4 ASJ
AF:
0.0130
Gnomad4 EAS
AF:
0.0244
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00115
Gnomad4 OTH
AF:
0.0114
Alfa
AF:
0.00799
Hom.:
7
Bravo
AF:
0.0170
Asia WGS
AF:
0.0150
AC:
53
AN:
3478
EpiCase
AF:
0.00164
EpiControl
AF:
0.00184

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMay 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
Cadd
Benign
0.23
Dann
Benign
0.37

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs56353131; hg19: chr12-106461213; COSMIC: COSV54607959; COSMIC: COSV54607959; API