rs759485888
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000314.8(PTEN):c.360A>C(p.Ala120=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,450 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 Likely benign (★★★). Synonymous variant affecting the same amino acid position (i.e. A120A) has been classified as Likely benign.
Frequency
Consequence
NM_000314.8 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.360A>C | p.Ala120= | synonymous_variant | 5/9 | ENST00000371953.8 | |
PTEN | NM_001304717.5 | c.879A>C | p.Ala293= | synonymous_variant | 6/10 | ||
PTEN | NM_001304718.2 | c.-391A>C | 5_prime_UTR_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.360A>C | p.Ala120= | synonymous_variant | 5/9 | 1 | NM_000314.8 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251254Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135788
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461284Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727008
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:3
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Nov 15, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 22, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 30, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
PTEN hamartoma tumor syndrome Benign:2
Likely benign, reviewed by expert panel | curation | Clingen PTEN Variant Curation Expert Panel, Clingen | Dec 14, 2016 | PTEN c.360A>C (p.A120=) meets criteria to be classified as likely benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (Mester et al. 2018; manuscript in preparation). Please see a summary of the rules and criteria codes in the 'PTEN ACMG Specifications Summary' document (assertion method column). BP4: Synonymous variant where at least 2 out of 3 in silico models predict no splicing impact. BP7: Variant is synonymous (silent), nucleotide is not conserved, and no splicing impact is predicted. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 14, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 18, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at