dbSNP rs823114: NUCKS1:c.-431C>T (chr1-205750404-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_022731.5(NUCKS1):c.-431C>T variant causes a upstream gene change. The variant allele was found at a frequency of 0.462 in 188,584 control chromosomes in the GnomAD database, including 22,359 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 0.45 ( 17406 hom., cov: 30)

Exomes 𝑓: 0.49 ( 4953 hom. )

Consequence

NUCKS1
NM_022731.5 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.32

Variant links:

Genes affected

NUCKS1 (HGNC:29923): (nuclear casein kinase and cyclin dependent kinase substrate 1) This gene encodes a nuclear protein that is highly conserved in vertebrates. The conserved regions of the protein contain several consensus phosphorylation sites for casein kinase II and cyclin-dependent kinases, two putative nuclear localization signals, and a basic DNA-binding domain. It is phosphorylated in vivo by Cdk1 during mitosis of the cell cycle. [provided by RefSeq, Aug 2010]

NUCKS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUCKS1	NM_022731.5 link	c.-431C>T		upstream_gene_variant		ENST00000367142.5	NP_073568.2	Q9H1E3-1
NUCKS1	XM_005245453.2 link	c.-431C>T		upstream_gene_variant			XP_005245510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUCKS1	ENST00000367142.5 link	c.-431C>T		upstream_gene_variant		1	NM_022731.5	ENSP00000356110.4		Q9H1E3-1

Frequencies

GnomAD3 genomes

AF:

0.454

AC:

68926

AN:

151668

Hom.:

17403

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.555

Gnomad AMR

AF:

0.435

Gnomad ASJ

AF:

0.584

Gnomad EAS

AF:

0.539

Gnomad SAS

AF:

0.526

Gnomad FIN

AF:

0.591

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.554

Gnomad OTH

AF:

0.482

GnomAD4 exome

AF:

0.494

AC:

18177

AN:

36798

Hom.:

4953

AF XY:

0.492

AC XY:

9764

AN XY:

19828

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.362

Gnomad4 ASJ exome

AF:

0.545

Gnomad4 EAS exome

AF:

0.434

Gnomad4 SAS exome

AF:

0.501

Gnomad4 FIN exome

AF:

0.550

Gnomad4 NFE exome

AF:

0.513

Gnomad4 OTH exome

AF:

0.462

GnomAD4 genome

AF:

0.454

AC:

68937

AN:

151786

Hom.:

17406

Cov.:

AF XY:

0.456

AC XY:

33811

AN XY:

74138

show subpopulations

Gnomad4 AFR

AF:

0.229

Gnomad4 AMR

AF:

0.435

Gnomad4 ASJ

AF:

0.584

Gnomad4 EAS

AF:

0.538

Gnomad4 SAS

AF:

0.526

Gnomad4 FIN

AF:

0.591

Gnomad4 NFE

AF:

0.554

Gnomad4 OTH

AF:

0.487

Alfa

AF:

0.543

Hom.:

33190

Bravo

AF:

0.430

Asia WGS

AF:

0.512

AC:

1783

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.93

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over