rs759872307
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_020975.6(RET):c.144G>A(p.Thr48=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,613,734 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. T48T) has been classified as Likely benign.
Frequency
Consequence
NM_020975.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RET | NM_020975.6 | c.144G>A | p.Thr48= | synonymous_variant | 2/20 | ENST00000355710.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RET | ENST00000355710.8 | c.144G>A | p.Thr48= | synonymous_variant | 2/20 | 5 | NM_020975.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152156Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250296Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135436
GnomAD4 exome AF: 0.0000547 AC: 80AN: 1461578Hom.: 0 Cov.: 64 AF XY: 0.0000619 AC XY: 45AN XY: 727060
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74316
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia type 2A;C0025269:Multiple endocrine neoplasia type 2B;C0031511:Pheochromocytoma;C1833921:Familial medullary thyroid carcinoma;C3888239:Hirschsprung disease, susceptibility to, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 30, 2021 | - - |
Multiple endocrine neoplasia, type 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 03, 2018 | 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. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 28, 2019 | 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. - |
RET-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 24, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at