Variant 12-106067435-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

NUAK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.06 with no splicing effect.

BS1

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

High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUAK1	NM_014840.3 linkuse as main transcript	c.1353G>A	p.Pro451=	synonymous_variant	7/7	ENST00000261402.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUAK1	ENST00000261402.7 linkuse as main transcript	c.1353G>A	p.Pro451=	synonymous_variant	7/7	1	NM_014840.3	P1	O60285-1

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2282

AN:

152134

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.0150

AC:

2290

AN:

152252

Hom.:

Cov.:

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.:

Bravo

AF:

0.0170

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over