rs757087471
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP2BP4
The NM_000314.8(PTEN):c.440A>G(p.Lys147Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,608 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 (★★). Synonymous variant affecting the same amino acid position (i.e. KA147K?) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000314.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.440A>G | p.Lys147Arg | missense_variant | 5/9 | ENST00000371953.8 | |
PTEN | NM_001304717.5 | c.959A>G | p.Lys320Arg | missense_variant | 6/10 | ||
PTEN | NM_001304718.2 | c.-311A>G | 5_prime_UTR_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.440A>G | p.Lys147Arg | missense_variant | 5/9 | 1 | NM_000314.8 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251264Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135822
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461608Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727108
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
PTEN hamartoma tumor syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 19, 2022 | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 490113). This variant has not been reported in the literature in individuals affected with PTEN-related conditions. This variant is present in population databases (rs757087471, gnomAD 0.003%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 147 of the PTEN protein (p.Lys147Arg). - |
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | May 04, 2023 | This missense variant replaces lysine with arginine at codon 147 of the PTEN protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PTEN-related disorders in the literature. This variant has been identified in 3/251264 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 18, 2019 | The p.K147R variant (also known as c.440A>G), located in coding exon 5 of the PTEN gene, results from an A to G substitution at nucleotide position 440. The lysine at codon 147 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 06, 2023 | This missense variant replaces lysine with arginine at codon 147 of the PTEN protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PTEN-related disorders in the literature. This variant has been identified in 3/251264 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Feb 06, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at