1-205720679-T-G

Variant names:

• chr1-205720679-T-G
• rs823094
• NM_022731.5:c.230-26A>C

Variant summary

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

The NM_022731.5(NUCKS1):​c.230-26A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,576,890 control chromosomes in the GnomAD database, including 123,033 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.34 (9777 hom., cov: 32)
  • Exomes 𝑓: 0.39 (113256 hom.)
• Consequence: NUCKS1 NM_022731.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200

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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUCKS1	NM_022731.5	c.230-26A>C		intron_variant	Intron 4 of 6	ENST00000367142.5	NP_073568.2
NUCKS1	XM_005245453.2	c.230-26A>C		intron_variant	Intron 4 of 6		XP_005245510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUCKS1	ENST00000367142.5	c.230-26A>C		intron_variant	Intron 4 of 6	1	NM_022731.5	ENSP00000356110.4

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51209 AN: 151984 Hom.: 9783 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.359

GnomAD3 exomes AF: 0.325 AC: 74256 AN: 228830 Hom.: 14377 AF XY: 0.328 AC XY: 40649 AN XY: 123986

Gnomad AFR exome AF: 0.233

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.429

Gnomad EAS exome AF: 0.00111

Gnomad SAS exome AF: 0.164

Gnomad FIN exome AF: 0.442

Gnomad NFE exome AF: 0.428

Gnomad OTH exome AF: 0.359

GnomAD4 exome AF: 0.385 AC: 548901 AN: 1424788 Hom.: 113256 Cov.: 26 AF XY: 0.379 AC XY: 268562 AN XY: 708054

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.427

Gnomad4 EAS exome AF: 0.00106

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.443

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.359

GnomAD4 genome AF: 0.337 AC: 51224 AN: 152102 Hom.: 9777 Cov.: 32 AF XY: 0.330 AC XY: 24504 AN XY: 74348

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.00443

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.354

Alfa AF: 0.374 Hom.: 5466

Bravo AF: 0.321

Asia WGS AF: 0.0820 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.61
BranchPoint Hunter		2.0

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: rs823094; hg19: chr1-205689807;