chr10-87863421-CCCCTG-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001126049.2(KLLN):c.-939_-935del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000687 in 218,290 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000069 ( 0 hom. )
Consequence
KLLN
NM_001126049.2 5_prime_UTR
NM_001126049.2 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.21
Genes affected
KLLN (HGNC:37212): (killin, p53 regulated DNA replication inhibitor) The protein encoded by this intronless gene is found in the nucleus, where it can inhibit DNA synthesis and promote S phase arrest coupled to apoptosis. The expression of this DNA binding protein is upregulated by transcription factor p53. [provided by RefSeq, Dec 2012]
PTEN (HGNC:9588): (phosphatase and tensin homolog) This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The use of a non-canonical (CUG) upstream initiation site produces a longer isoform that initiates translation with a leucine, and is thought to be preferentially associated with the mitochondrial inner membrane. This longer isoform may help regulate energy metabolism in the mitochondria. A pseudogene of this gene is found on chromosome 9. Alternative splicing and the use of multiple translation start codons results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLLN | NM_001126049.2 | c.-939_-935del | 5_prime_UTR_variant | 1/1 | ENST00000445946.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLLN | ENST00000445946.5 | c.-939_-935del | 5_prime_UTR_variant | 1/1 | NM_001126049.2 | P1 | |||
PTEN | ENST00000688308.1 | c.-17+323_-17+327del | intron_variant | P1 | |||||
PTEN | ENST00000693560.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.0000687 AC: 15AN: 218290Hom.: 0 AF XY: 0.0000721 AC XY: 8AN XY: 110944
GnomAD4 exome
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15
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218290
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8
AN XY:
110944
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 02, 2018 | This variant is denoted PTEN c.-1034_-1030delGCCCT, and describes a deletion of 5 nucleotides in the PTEN promoter region. The surrounding sequence, with the bases deleted in brackets, is CCCT[delGCCCT]CCCCT. This variant, also called c.-1033_-1029delGCCCT using alternate numbering, has not been published in the literature to our knowledge. Variants within the PTEN promoter have been observed in individuals with features of Cowden syndrome (Zhou 2003). At this time, we consider this to be a variant of uncertain significance. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2014 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at