chr1-205750014-C-CCGGGGGGGGGGGGGGGGGGGGGGGGG

Position:

• chr1-205750014-C-CCGGGGGGGGGGGGGGGGGGGGGGGGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022731.5(NUCKS1):​c.-42_-41insCCCCCCCCCCCCCCCCCCCCCCCCCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 1,420,160 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: NUCKS1 NM_022731.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.390

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUCKS1	NM_022731.5	c.-42_-41insCCCCCCCCCCCCCCCCCCCCCCCCCG		5_prime_UTR_variant	1/7	ENST00000367142.5	NP_073568.2
NUCKS1	XM_005245453.2	c.-42_-41insCCCCCCCCCCCCCCCCCCCCCCCCCG		5_prime_UTR_variant	1/7		XP_005245510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUCKS1	ENST00000367142.5	c.-42_-41insCCCCCCCCCCCCCCCCCCCCCCCCCG		5_prime_UTR_variant	1/7	1	NM_022731.5	ENSP00000356110.4

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.0000176 AC: 25 AN: 1420160 Hom.: 0 Cov.: 32 AF XY: 0.0000170 AC XY: 12 AN XY: 705710

Gnomad4 AFR exome AF: 0.0000621

Gnomad4 AMR exome AF: 0.0000235

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000273

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000396

Gnomad4 NFE exome AF: 0.0000129

Gnomad4 OTH exome AF: 0.0000866

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-205719142;