1-205725592-G-A

Variant names:

• chr1-205725592-G-A
• rs3761919
• NM_022731.5:c.174-1611C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUCKS1	NM_022731.5	MANE Select	c.174-1611C>T		intron	N/A	NP_073568.2	Q9H1E3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUCKS1	ENST00000367142.5	TSL:1 MANE Select	c.174-1611C>T		intron	N/A	ENSP00000356110.4	Q9H1E3-1
	NUCKS1	ENST00000875217.1		c.174-1611C>T		intron	N/A	ENSP00000545276.1
	NUCKS1	ENST00000875218.1		c.168-1611C>T		intron	N/A	ENSP00000545277.1

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

African (AFR) AF: 0.122 AC: 5060 AN: 41396

American (AMR) AF: 0.323 AC: 4925 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 648 AN: 3470

East Asian (EAS) AF: 0.314 AC: 1624 AN: 5170

South Asian (SAS) AF: 0.260 AC: 1250 AN: 4810

European-Finnish (FIN) AF: 0.215 AC: 2261 AN: 10514

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.259 AC: 17619 AN: 67944

Other (OTH) AF: 0.217 AC: 456 AN: 2098

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.72
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3761919; hg19: chr1-205694720;