Variant chr5-134161122-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_170679.3(SKP1):c.180G>C(p.Gln60His) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,212 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SKP1
NM_170679.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68

Variant links:

Genes affected

SKP1 (HGNC:10899): (S-phase kinase associated protein 1) This gene encodes a component of SCF complexes, which are composed of this protein, cullin 1, a ring-box protein, and one member of the F-box family of proteins. This protein binds directly to the F-box motif found in F-box proteins. SCF complexes are involved in the regulated ubiquitination of specific protein substrates, which targets them for degradation by the proteosome. Specific F-box proteins recognize different target protein(s), and many specific SCF substrates have been identified including regulators of cell cycle progression and development. Studies have also characterized the protein as an RNA polymerase II elongation factor. Alternative splicing of this gene results in two transcript variants. A related pseudogene has been identified on chromosome 7. [provided by RefSeq, Jul 2008]

SKP1 links:

ENSG00000272772 (HGNC:):

ENSG00000272772 links:

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ACMG classification

Classification made for transcript

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
SKP1	NM_170679.3 linkuse as main transcript	c.180G>C	p.Gln60His	missense_variant	4/6	ENST00000353411.11	NP_733779.1	P63208-1
SKP1	NM_006930.4 linkuse as main transcript	c.180G>C	p.Gln60His	missense_variant	4/5		NP_008861.2	P63208-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKP1	ENST00000353411.11 linkuse as main transcript	c.180G>C	p.Gln60His	missense_variant	4/6	1	NM_170679.3	ENSP00000231487.9		P63208-1
ENSG00000272772	ENST00000519718.2 linkuse as main transcript	c.282G>C	p.Gln94His	missense_variant	4/6	5		ENSP00000430774.2		E5RI56

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

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

May 26, 2023

The c.180G>C (p.Q60H) alteration is located in exon 4 (coding exon 3) of the SKP1 gene. This alteration results from a G to C substitution at nucleotide position 180, causing the glutamine (Q) at amino acid position 60 to be replaced by a histidine (H). 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

Uncertain

0.47

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.062

T;.;T;T;T;T;.;T

Eigen

Benign

-0.090

Eigen_PC

Benign

0.052

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

.;D;D;.;D;D;D;D

M_CAP

Benign

0.0035

MetaRNN

Uncertain

0.46

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;.;L;L;.;.;.

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.9

N;N;N;N;N;N;N;N

REVEL

Benign

0.24

Sift

Benign

0.092

T;T;T;T;T;T;T;T

Sift4G

Uncertain

0.034

D;D;D;D;D;.;.;T

Polyphen

0.0

B;B;B;B;B;.;.;.

Vest4

0.71

MutPred

0.57

Gain of methylation at K56 (P = 0.1741);Gain of methylation at K56 (P = 0.1741);Gain of methylation at K56 (P = 0.1741);Gain of methylation at K56 (P = 0.1741);Gain of methylation at K56 (P = 0.1741);Gain of methylation at K56 (P = 0.1741);Gain of methylation at K56 (P = 0.1741);Gain of methylation at K56 (P = 0.1741);

MVP

0.51

MPC

2.1

ClinPred

0.78

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.53

gMVP

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over