12-57748221-TAAAAA-TA

Variant names:

• chr12-57748221-TAAAA-T
• rs59185470
• NM_000075.4:c.*300_*303delTTTT

Variant summary

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

The NM_000075.4(CDK4):​c.*300_*303delTTTT 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
• 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]

ACMG classification

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
CDK4	NM_000075.4	c.*300_*303delTTTT		3_prime_UTR_variant	Exon 8 of 8	ENST00000257904.11	NP_000066.1
TSPAN31	NM_005981.5	c.*942_*945delAAAA		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.*300_*303delTTTT		3_prime_UTR_variant	Exon 8 of 8	1	NM_000075.4	ENSP00000257904.5
TSPAN31	ENST00000257910.8	c.*942_*945delAAAA		3_prime_UTR_variant	Exon 6 of 6	1	NM_005981.5	ENSP00000257910.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 188948 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 97134

African (AFR) AF: 0.00 AC: 0 AN: 6692

American (AMR) AF: 0.00 AC: 0 AN: 6594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7186

East Asian (EAS) AF: 0.00 AC: 0 AN: 15456

South Asian (SAS) AF: 0.00 AC: 0 AN: 22328

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5464

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 830

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 112814

Other (OTH) AF: 0.00 AC: 0 AN: 11584

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

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: rs59185470; hg19: chr12-58142004;