Variant 1-205727805-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_022731.5(NUCKS1):c.68A>G(p.Asp23Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000208 in 1,444,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NUCKS1
NM_022731.5 missense, splice_region

Scores

Splicing: ADA: 0.6616

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09

Variant links:

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]

NUCKS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.803

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUCKS1	NM_022731.5 linkuse as main transcript	c.68A>G	p.Asp23Gly	missense_variant, splice_region_variant	3/7	ENST00000367142.5	NP_073568.2	Q9H1E3-1
NUCKS1	XM_005245453.2 linkuse as main transcript	c.68A>G	p.Asp23Gly	missense_variant, splice_region_variant	3/7		XP_005245510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUCKS1	ENST00000367142.5 linkuse as main transcript	c.68A>G	p.Asp23Gly	missense_variant, splice_region_variant	3/7	1	NM_022731.5	ENSP00000356110.4		Q9H1E3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1444396

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719952

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000273

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2022

The c.68A>G (p.D23G) alteration is located in exon 3 (coding exon 3) of the NUCKS1 gene. This alteration results from a A to G substitution at nucleotide position 68, causing the aspartic acid (D) at amino acid position 23 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.043

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-0.35

MutationAssessor

Uncertain

2.8

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.35

Sift

Uncertain

0.0040

Sift4G

Benign

0.14

Polyphen

0.99

Vest4

0.85

MutPred

0.31

Loss of stability (P = 0.0529);

MVP

0.63

MPC

1.5

ClinPred

0.99

GERP RS

5.6

Varity_R

0.49

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.66

dbscSNV1_RF

Benign

0.71

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over