GeneBe

12-57747747-CTTTT-CTTTTTTTT

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000075.4(CDK4):​c.*774_*777dupAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CDK4
NM_000075.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.674

Publications

0 publications found
Variant links:
Genes affected
CDK4 (HGNC:1773): (cyclin dependent kinase 4) The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported. [provided by RefSeq, Jul 2008]
TSPAN31 (HGNC:10539): (tetraspanin 31) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is thought to be involved in growth-related cellular processes. This gene is associated with tumorigenesis and osteosarcoma. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDK4NM_000075.4 linkc.*774_*777dupAAAA 3_prime_UTR_variant Exon 8 of 8 ENST00000257904.11 NP_000066.1 P11802-1A0A024RBB6
TSPAN31NM_005981.5 linkc.*467_*470dupTTTT 3_prime_UTR_variant Exon 6 of 6 ENST00000257910.8 NP_005972.1 Q12999

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDK4ENST00000257904.11 linkc.*774_*777dupAAAA 3_prime_UTR_variant Exon 8 of 8 1 NM_000075.4 ENSP00000257904.5 P11802-1
TSPAN31ENST00000257910.8 linkc.*467_*470dupTTTT 3_prime_UTR_variant Exon 6 of 6 1 NM_005981.5 ENSP00000257910.3 Q12999

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
4916
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
2402
African (AFR)
AF:
0.00
AC:
0
AN:
78
American (AMR)
AF:
0.00
AC:
0
AN:
396
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
240
East Asian (EAS)
AF:
0.00
AC:
0
AN:
634
South Asian (SAS)
AF:
0.00
AC:
0
AN:
234
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
16
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
26
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
3024
Other (OTH)
AF:
0.00
AC:
0
AN:
268
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
-0.67

Splicing

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

Publications

Other links and lift over

dbSNP: rs146863045; hg19: chr12-58141530; API