rs3804443

Variant names:

• chr5-36157710-G-A
• rs3804443
• NM_005983.4:c.280+4668G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005983.4(SKP2):​c.280+4668G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,190 control chromosomes in the GnomAD database, including 1,324 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 0.12 (1324 hom., cov: 33)
• Consequence: SKP2 NM_005983.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 1 publications found

Genes affected

SKP2 (HGNC:10901): (S-phase kinase associated protein 2) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class; in addition to an F-box, this protein contains 10 tandem leucine-rich repeats. This protein is an essential element of the cyclin A-CDK2 S-phase kinase. It specifically recognizes phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also referred to as p27 or KIP1) predominantly in S phase and interacts with S-phase kinase-associated protein 1 (SKP1 or p19). In addition, this gene is established as a protooncogene causally involved in the pathogenesis of lymphomas. Alternative splicing of this gene generates three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005983.4. 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
	SKP2	NM_005983.4	MANE Select	c.280+4668G>A		intron	N/A	NP_005974.2
	SKP2	NM_032637.4		c.280+4668G>A		intron	N/A	NP_116026.1
	SKP2	NM_001243120.2		c.-116+4668G>A		intron	N/A	NP_001230049.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKP2	ENST00000274255.11	TSL:1 MANE Select	c.280+4668G>A		intron	N/A	ENSP00000274255.6
	SKP2	ENST00000274254.9	TSL:1	c.280+4668G>A		intron	N/A	ENSP00000274254.5
	SKP2	ENST00000546211.6	TSL:5	c.281-2063G>A		intron	N/A	ENSP00000443492.3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18196 AN: 152072 Hom.: 1314 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0763

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.120 AC: 18237 AN: 152190 Hom.: 1324 Cov.: 33 AF XY: 0.117 AC XY: 8686 AN XY: 74436

African (AFR) AF: 0.191 AC: 7925 AN: 41486

American (AMR) AF: 0.0761 AC: 1164 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 522 AN: 3472

East Asian (EAS) AF: 0.0526 AC: 273 AN: 5190

South Asian (SAS) AF: 0.168 AC: 808 AN: 4822

European-Finnish (FIN) AF: 0.0648 AC: 687 AN: 10594

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0957 AC: 6510 AN: 68010

Other (OTH) AF: 0.123 AC: 260 AN: 2112

Alfa AF: 0.108 Hom.: 293

Bravo AF: 0.123

Asia WGS AF: 0.145 AC: 506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.25
PhyloP100		0.026
Mutation Taster		=100/0	polymorphism (auto)

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: rs3804443; hg19: chr5-36157812;