chr10-87863482-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001126049.2(KLLN):c.-995G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 230,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001126049.2 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KLLN | ENST00000445946.5 | c.-995G>A | 5_prime_UTR_variant | Exon 1 of 1 | 6 | NM_001126049.2 | ENSP00000392204.2 | |||
PTEN | ENST00000693560 | c.-468C>T | 5_prime_UTR_variant | Exon 1 of 10 | ENSP00000509861.1 | |||||
PTEN | ENST00000688308.1 | c.-17+369C>T | intron_variant | Intron 1 of 9 | ENSP00000508752.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000434 AC: 1AN: 230462Hom.: 0 Cov.: 0 AF XY: 0.00000853 AC XY: 1AN XY: 117276
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
PTEN-related disorder Uncertain:1
The PTEN c.-987C>T variant is located in the 5' untranslated region. The PTEN gene variant c.-987C>T (referred to by alternative nomenclature as c.-986C>T) is located in the PTEN promoter region. To our knowledge, this variant has not been reported in the literature. However, variants within the PTEN promoter have been observed in individuals with Cowden syndrome (Zhou et al. 2003. PubMed ID: 12844284; Tan et al. 2011. PubMed ID: 21194675). This variant has been observed in only 1 out of ~30,900 alleles in the gnomAD v2 database and has conflicting interpretations in ClinVar as uncertain and likely benign. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
not provided Uncertain:1
The PTEN c.-987C>T variant has not been reported in individuals with PTEN-related conditions in the published literature. The frequency of this variant in the general population, 0.000032 (1/31308 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant. -
Hereditary cancer-predisposing syndrome Uncertain:1
The c.-987C>T variant is located in the 5' untranslated region (5’ UTR) of the PTEN gene. This variant results from a C to T substitution 987 nucleotides upstream of the first translated codon. This variant is located in the promoter region of the PTEN gene, but its potential impact on PTEN regulation has not yet been investigated (Zhou XP et al. Am. J. Hum. Genet. 2003 Aug;73:404-11). This nucleotide position is highly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at