rs201568301
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_020975.6(RET):c.1353G>A(p.Thr451=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,048 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. T451T) 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 -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RET | NM_020975.6 | c.1353G>A | p.Thr451= | synonymous_variant | 7/20 | ENST00000355710.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RET | ENST00000355710.8 | c.1353G>A | p.Thr451= | synonymous_variant | 7/20 | 5 | NM_020975.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152242Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251460Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135912
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461806Hom.: 0 Cov.: 58 AF XY: 0.0000110 AC XY: 8AN XY: 727202
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152242Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74392
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 06, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 04, 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. - |
Multiple endocrine neoplasia, type 2 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 25, 2020 | 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