rs3761919

chr1-205725592-G-Achr1-205725592-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022731.5(NUCKS1):c.174-1611C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,870 control chromosomes in the GnomAD database, including 4,333 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 0.22 (4333 hom., cov: 32)
• Consequence: NUCKS1 NM_022731.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUCKS1	NM_022731.5	c.174-1611C>T		intron_variant		ENST00000367142.5
NUCKS1	XM_005245453.2	c.174-1611C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUCKS1	ENST00000367142.5	c.174-1611C>T		intron_variant		1	NM_022731.5	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34151 AN: 151754 Hom.: 4328 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.220

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.225 AC: 34160 AN: 151870 Hom.: 4333 Cov.: 32 AF XY: 0.225 AC XY: 16672 AN XY: 74176

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.217

Alfa AF: 0.234 Hom.: 1286

Bravo AF: 0.229

Asia WGS AF: 0.271 AC: 940 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.6
Dann	Benign	0.72

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

Other links and lift over

dbSNP: rs3761919; hg19: chr1-205694720;