rs823128

Positions:

• chr1-205744250-G-A
• chr1-205744250-G-C
• chr1-205744250-G-T

Variant summary

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

The NM_022731.5(NUCKS1):​c.17+5707C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,244 control chromosomes in the GnomAD database, including 59,927 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 0.88 (59927 hom., cov: 33)
• Consequence: NUCKS1 NM_022731.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUCKS1	NM_022731.5	c.17+5707C>T		intron_variant		ENST00000367142.5	NP_073568.2
NUCKS1	XM_005245453.2	c.17+5707C>T		intron_variant			XP_005245510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUCKS1	ENST00000367142.5	c.17+5707C>T		intron_variant		1	NM_022731.5	ENSP00000356110	P1

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133889 AN: 152126 Hom.: 59898 Cov.: 33

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.886

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

GnomAD4 genome AF: 0.880 AC: 133979 AN: 152244 Hom.: 59927 Cov.: 33 AF XY: 0.880 AC XY: 65486 AN XY: 74436

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.912

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.891

Gnomad4 FIN AF: 0.969

Gnomad4 NFE AF: 0.966

Gnomad4 OTH AF: 0.886

Alfa AF: 0.946 Hom.: 151779

Bravo AF: 0.864

Asia WGS AF: 0.865 AC: 3011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.76

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: rs823128; hg19: chr1-205713378;