chr10-43119547-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_020975.6(RET):c.2409C>T(p.Ile803=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000698 in 1,605,180 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. I803I) 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.2409C>T | p.Ile803= | synonymous_variant | 14/20 | ENST00000355710.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RET | ENST00000355710.8 | c.2409C>T | p.Ile803= | synonymous_variant | 14/20 | 5 | NM_020975.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152194Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000173 AC: 4AN: 231384Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 127186
GnomAD4 exome AF: 0.0000681 AC: 99AN: 1452870Hom.: 0 Cov.: 33 AF XY: 0.0000720 AC XY: 52AN XY: 722562
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152310Hom.: 0 Cov.: 34 AF XY: 0.000121 AC XY: 9AN XY: 74464
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia type 2A Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Nov 20, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Apr 18, 2023 | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. - |
Multiple endocrine neoplasia type 2B Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Nov 20, 2015 | - - |
Multiple endocrine neoplasia, type 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 18, 2016 | 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 05, 2024 | 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