chr1-205725235-G-C

Variant names:

• chr1-205725235-G-C
• rs10494873
• NM_022731.5:c.174-1254C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_022731.5(NUCKS1):​c.174-1254C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 152,218 control chromosomes in the GnomAD database, including 58 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 0.017 (58 hom., cov: 32)
• Consequence: NUCKS1 NM_022731.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303
• Publications: 2 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=-0.9).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0171 (2609/152218) while in subpopulation AFR AF = 0.0454 (1886/41528). AF 95% confidence interval is 0.0437. There are 58 homozygotes in GnomAd4. There are 1228 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 58 gene

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.174-1254C>G		intron	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.174-1254C>G		intron	N/A	ENSP00000356110.4

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2594 AN: 152100 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00949

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00142

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00613

Gnomad OTH AF: 0.0153

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

GnomAD4 genome AF: 0.0171 AC: 2609 AN: 152218 Hom.: 58 Cov.: 32 AF XY: 0.0165 AC XY: 1228 AN XY: 74418

African (AFR) AF: 0.0454 AC: 1886 AN: 41528

American (AMR) AF: 0.00948 AC: 145 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3468

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00142 AC: 15 AN: 10590

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00613 AC: 417 AN: 68018

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.00112 Hom.: 0

Bravo AF: 0.0192

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.84
DANN	Benign	0.59
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

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: rs10494873; hg19: chr1-205694363;