chr10-43111380-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.1437C>T(p.Ala479=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,614,000 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. A479A) 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.1437C>T | p.Ala479= | synonymous_variant | 7/20 | ENST00000355710.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RET | ENST00000355710.8 | c.1437C>T | p.Ala479= | synonymous_variant | 7/20 | 5 | NM_020975.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152196Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000131 AC: 33AN: 251308Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135874
GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461686Hom.: 0 Cov.: 57 AF XY: 0.0000399 AC XY: 29AN XY: 727148
GnomAD4 genome AF: 0.000118 AC: 18AN: 152314Hom.: 0 Cov.: 34 AF XY: 0.000107 AC XY: 8AN XY: 74466
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia, type 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 13, 2023 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | RET: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 05, 2017 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 16, 2015 | 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. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Jun 17, 2021 | - - |
Multiple endocrine neoplasia type 2B Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Dec 09, 2015 | - - |
Multiple endocrine neoplasia type 2A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Dec 09, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at