rs397516798
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_002834.5(PTPN11):c.1683G>A(p.Pro561=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,482 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 (★★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
PTPN11
NM_002834.5 synonymous
NM_002834.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.708
Genes affected
PTPN11 (HGNC:9644): (protein tyrosine phosphatase non-receptor type 11) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains two tandem Src homology-2 domains, which function as phospho-tyrosine binding domains and mediate the interaction of this PTP with its substrates. This PTP is widely expressed in most tissues and plays a regulatory role in various cell signaling events that are important for a diversity of cell functions, such as mitogenic activation, metabolic control, transcription regulation, and cell migration. Mutations in this gene are a cause of Noonan syndrome as well as acute myeloid leukemia. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant 12-112502227-G-A is Benign according to our data. Variant chr12-112502227-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 44600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPN11 | NM_002834.5 | c.1683G>A | p.Pro561= | synonymous_variant | 14/16 | ENST00000351677.7 | |
PTPN11 | NM_001330437.2 | c.1695G>A | p.Pro565= | synonymous_variant | 14/16 | ||
PTPN11 | NM_001374625.1 | c.1680G>A | p.Pro560= | synonymous_variant | 14/16 | ||
PTPN11 | XM_011538613.3 | c.1692G>A | p.Pro564= | synonymous_variant | 14/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPN11 | ENST00000351677.7 | c.1683G>A | p.Pro561= | synonymous_variant | 14/16 | 1 | NM_002834.5 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152066Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251078Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135684
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461416Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727054
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GnomAD4 genome AF: 0.0000395 AC: 6AN: 152066Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74270
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 19, 2015 | p.Pro561Pro in exon 14 of PTPN11: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 2/16494 South As ian chromosomes, 1/10356 African chromosomes, and 1/11558 Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 397516798). - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2023 | 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. - |
RASopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at