1-205725235-G-C

Position:

• chr1-205725235-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 58 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUCKS1	NM_022731.5	c.174-1254C>G		intron_variant		ENST00000367142.5	NP_073568.2
NUCKS1	XM_005245453.2	c.174-1254C>G		intron_variant			XP_005245510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUCKS1	ENST00000367142.5	c.174-1254C>G		intron_variant		1	NM_022731.5	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

Gnomad4 AFR AF: 0.0454

Gnomad4 AMR AF: 0.00948

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00142

Gnomad4 NFE AF: 0.00613

Gnomad4 OTH AF: 0.0152

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.84
DANN	Benign	0.59

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: rs10494873; hg19: chr1-205694363;