12-57748221-TAAAAA-TAA
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
The NM_000075.4(CDK4):c.*301_*303delTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000635 in 188,872 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000064 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CDK4
NM_000075.4 3_prime_UTR
NM_000075.4 3_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.37
Publications
0 publications found
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CDK4 | NM_000075.4 | c.*301_*303delTTT | 3_prime_UTR_variant | Exon 8 of 8 | ENST00000257904.11 | NP_000066.1 | ||
| TSPAN31 | NM_005981.5 | c.*943_*945delAAA | 3_prime_UTR_variant | Exon 6 of 6 | ENST00000257910.8 | NP_005972.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CDK4 | ENST00000257904.11 | c.*301_*303delTTT | 3_prime_UTR_variant | Exon 8 of 8 | 1 | NM_000075.4 | ENSP00000257904.5 | |||
| TSPAN31 | ENST00000257910.8 | c.*943_*945delAAA | 3_prime_UTR_variant | Exon 6 of 6 | 1 | NM_005981.5 | ENSP00000257910.3 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 137160Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
0
AN:
137160
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000635 AC: 12AN: 188872Hom.: 0 AF XY: 0.0000721 AC XY: 7AN XY: 97084 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
12
AN:
188872
Hom.:
AF XY:
AC XY:
7
AN XY:
97084
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
6690
American (AMR)
AF:
AC:
0
AN:
6590
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
7182
East Asian (EAS)
AF:
AC:
1
AN:
15450
South Asian (SAS)
AF:
AC:
2
AN:
22318
European-Finnish (FIN)
AF:
AC:
2
AN:
5464
Middle Eastern (MID)
AF:
AC:
0
AN:
828
European-Non Finnish (NFE)
AF:
AC:
5
AN:
112770
Other (OTH)
AF:
AC:
1
AN:
11580
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.233
Heterozygous variant carriers
0
2
4
7
9
11
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00 AC: 0AN: 137160Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 66200
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
137160
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
66200
African (AFR)
AF:
AC:
0
AN:
37824
American (AMR)
AF:
AC:
0
AN:
13706
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3218
East Asian (EAS)
AF:
AC:
0
AN:
4828
South Asian (SAS)
AF:
AC:
0
AN:
4346
European-Finnish (FIN)
AF:
AC:
0
AN:
7726
Middle Eastern (MID)
AF:
AC:
0
AN:
284
European-Non Finnish (NFE)
AF:
AC:
0
AN:
62558
Other (OTH)
AF:
AC:
0
AN:
1838
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.