5-36178942-T-C

Variant names:

• chr5-36178942-T-C
• rs3804439
• NM_005983.4:c.1061+1650T>C

Variant summary

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

The NM_005983.4(SKP2):​c.1061+1650T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,044 control chromosomes in the GnomAD database, including 5,333 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 0.22 (5333 hom., cov: 32)
• Consequence: SKP2 NM_005983.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 14 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKP2	NM_005983.4	MANE Select	c.1061+1650T>C		intron	N/A	NP_005974.2
	SKP2	NM_032637.4		c.1061+1650T>C		intron	N/A	NP_116026.1	Q13309-2
	SKP2	NM_001243120.2		c.419+1650T>C		intron	N/A	NP_001230049.1	Q13309-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKP2	ENST00000274255.11	TSL:1 MANE Select	c.1061+1650T>C		intron	N/A	ENSP00000274255.6	Q13309-1
	SKP2	ENST00000274254.9	TSL:1	c.1061+1650T>C		intron	N/A	ENSP00000274254.5	Q13309-2
	SKP2	ENST00000678580.1		c.*329T>C		3_prime_UTR	Exon 10 of 10	ENSP00000504064.1	D6R9R7

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32820 AN: 151926 Hom.: 5312 Cov.: 32

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.216 AC: 32898 AN: 152044 Hom.: 5333 Cov.: 32 AF XY: 0.214 AC XY: 15881 AN XY: 74350

African (AFR) AF: 0.447 AC: 18534 AN: 41422

American (AMR) AF: 0.162 AC: 2479 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 766 AN: 3460

East Asian (EAS) AF: 0.216 AC: 1118 AN: 5166

South Asian (SAS) AF: 0.244 AC: 1179 AN: 4824

European-Finnish (FIN) AF: 0.0605 AC: 642 AN: 10616

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7645 AN: 67976

Other (OTH) AF: 0.204 AC: 431 AN: 2110

Alfa AF: 0.160 Hom.: 7953

Bravo AF: 0.236

Asia WGS AF: 0.249 AC: 865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.7
DANN	Benign	0.65
PhyloP100		-0.29
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: rs3804439; hg19: chr5-36179044;