chr1-205716224-T-C

Variant names:

• chr1-205716224-T-C
• rs951366
• NM_022731.5:c.*2056A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022731.5(NUCKS1):​c.*2056A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,928 control chromosomes in the GnomAD database, including 9,404 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 0.34 (9404 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: NUCKS1 NM_022731.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.982
• Publications: 50 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=-0.56).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUCKS1	NM_022731.5	c.*2056A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000367142.5	NP_073568.2
NUCKS1	XM_005245453.2	c.*2056A>G		3_prime_UTR_variant	Exon 7 of 7		XP_005245510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUCKS1	ENST00000367142.5	c.*2056A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_022731.5	ENSP00000356110.4

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52349 AN: 151810 Hom.: 9396 Cov.: 31

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.341

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.345 AC: 52382 AN: 151928 Hom.: 9404 Cov.: 31 AF XY: 0.344 AC XY: 25533 AN XY: 74252

African (AFR) AF: 0.261 AC: 10826 AN: 41452

American (AMR) AF: 0.411 AC: 6275 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1014 AN: 3472

East Asian (EAS) AF: 0.315 AC: 1628 AN: 5172

South Asian (SAS) AF: 0.339 AC: 1628 AN: 4806

European-Finnish (FIN) AF: 0.359 AC: 3781 AN: 10526

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26095 AN: 67922

Other (OTH) AF: 0.336 AC: 710 AN: 2110

Alfa AF: 0.359 Hom.: 6841

Bravo AF: 0.347

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.5
DANN	Benign	0.78
PhyloP100		0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs951366; hg19: chr1-205685352;