10-43100524-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_020975.6(RET):c.139G>A(p.Gly47Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,834 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G47R) has been classified as Uncertain significance.
Frequency
Consequence
NM_020975.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RET | NM_020975.6 | c.139G>A | p.Gly47Ser | missense_variant | 2/20 | ENST00000355710.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RET | ENST00000355710.8 | c.139G>A | p.Gly47Ser | missense_variant | 2/20 | 5 | NM_020975.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152124Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250006Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135306
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461592Hom.: 0 Cov.: 64 AF XY: 0.00000688 AC XY: 5AN XY: 727056
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74428
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 05, 2019 | - - |
Multiple endocrine neoplasia type 2A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Dec 13, 2016 | - - |
Multiple endocrine neoplasia, type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 31, 2023 | An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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: 241335). This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is present in population databases (rs529018971, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 47 of the RET protein (p.Gly47Ser). - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 15, 2022 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at