NM_022731.5:c.-431C>T

Variant names:

• chr1-205750404-G-A
• rs823114
• NM_022731.5:c.-431C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.32
• Publications: 78 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022731.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUCKS1	NM_022731.5	MANE Select	c.-431C>T		upstream_gene	N/A	NP_073568.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUCKS1	ENST00000367142.5	TSL:1 MANE Select	c.-431C>T		upstream_gene	N/A	ENSP00000356110.4

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68926 AN: 151668 Hom.: 17403 Cov.: 30

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

African (AFR) AF: 0.167 AC: 156 AN: 936

American (AMR) AF: 0.362 AC: 518 AN: 1432

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 531 AN: 974

East Asian (EAS) AF: 0.434 AC: 614 AN: 1414

South Asian (SAS) AF: 0.501 AC: 3146 AN: 6274

European-Finnish (FIN) AF: 0.550 AC: 1236 AN: 2248

Middle Eastern (MID) AF: 0.630 AC: 92 AN: 146

European-Non Finnish (NFE) AF: 0.513 AC: 10936 AN: 21322

Other (OTH) AF: 0.462 AC: 948 AN: 2052

GnomAD4 genome AF: 0.454 AC: 68937 AN: 151786 Hom.: 17406 Cov.: 30 AF XY: 0.456 AC XY: 33811 AN XY: 74138

African (AFR) AF: 0.229 AC: 9466 AN: 41392

American (AMR) AF: 0.435 AC: 6625 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2028 AN: 3470

East Asian (EAS) AF: 0.538 AC: 2762 AN: 5130

South Asian (SAS) AF: 0.526 AC: 2528 AN: 4804

European-Finnish (FIN) AF: 0.591 AC: 6212 AN: 10506

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37621 AN: 67936

Other (OTH) AF: 0.487 AC: 1024 AN: 2102

Alfa AF: 0.517 Hom.: 43894

Bravo AF: 0.430

Asia WGS AF: 0.512 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.93
PhyloP100		4.3
PromoterAI		-0.053	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs823114; hg19: chr1-205719532;