rs758644748
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP2BP4
The NM_000314.8(PTEN):c.901G>A(p.Asp301Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,612,844 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D301Y) has been classified as Uncertain significance.
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.901G>A | p.Asp301Asn | missense_variant | 8/9 | ENST00000371953.8 | |
PTEN | NM_001304717.5 | c.1420G>A | p.Asp474Asn | missense_variant | 9/10 | ||
PTEN | NM_001304718.2 | c.310G>A | p.Asp104Asn | missense_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.901G>A | p.Asp301Asn | missense_variant | 8/9 | 1 | NM_000314.8 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000661 AC: 1AN: 151334Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251222Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135774
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461510Hom.: 0 Cov.: 36 AF XY: 0.00000275 AC XY: 2AN XY: 727074
GnomAD4 genome ? AF: 0.00000661 AC: 1AN: 151334Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 73802
ClinVar
Submissions by phenotype
PTEN hamartoma tumor syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 01, 2023 | 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. Experimental studies have shown that this missense change affects PTEN function (PMID: 12788938, 19329485). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt PTEN function. ClinVar contains an entry for this variant (Variation ID: 233963). This variant has not been reported in the literature in individuals affected with PTEN-related conditions. This variant is present in population databases (rs758644748, gnomAD 0.01%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 301 of the PTEN protein (p.Asp301Asn). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | Jul 02, 2018 | - - |
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 23, 2020 | The c.901G>A (p.D301N) alteration is located in exon 8 (coding exon 8) of the PTEN gene. This alteration results from a G to A substitution at nucleotide position 901, causing the aspartic acid (D) at amino acid position 301 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 07, 2023 | This missense variant replaces aspartic acid with asparagine at codon 301 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). Functional studies have demonstrated a similar impact as wild-type in an AKT phosphorylation assay (PMID: 19329485). This variant has not been reported in individuals affected with hereditary cancer in the literature, but it also affects a Caspase cleavage site in the PTEN protein which may impair the regulation of protein stability (PMID: 12788938). This variant has been identified in 2/251222 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 provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jun 30, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at