10-43077236-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_020975.6(RET):c.-23C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000402 in 1,494,330 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 (★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 35)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
RET
NM_020975.6 5_prime_UTR
NM_020975.6 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.352
Genes affected
RET (HGNC:9967): (ret proto-oncogene) This gene encodes a transmembrane receptor and member of the tyrosine protein kinase family of proteins. Binding of ligands such as GDNF (glial cell-line derived neurotrophic factor) and other related proteins to the encoded receptor stimulates receptor dimerization and activation of downstream signaling pathways that play a role in cell differentiation, growth, migration and survival. The encoded receptor is important in development of the nervous system, and the development of organs and tissues derived from the neural crest. This proto-oncogene can undergo oncogenic activation through both cytogenetic rearrangement and activating point mutations. Mutations in this gene are associated with Hirschsprung disease and central hypoventilation syndrome and have been identified in patients with renal agenesis. [provided by RefSeq, Sep 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
Variant 10-43077236-C-T is Benign according to our data. Variant chr10-43077236-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3054907.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RET | NM_020975.6 | c.-23C>T | 5_prime_UTR_variant | 1/20 | ENST00000355710.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RET | ENST00000355710.8 | c.-23C>T | 5_prime_UTR_variant | 1/20 | 5 | NM_020975.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000197 AC: 30AN: 151982Hom.: 0 Cov.: 35
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GnomAD3 exomes AF: 0.0000305 AC: 3AN: 98278Hom.: 0 AF XY: 0.0000182 AC XY: 1AN XY: 54868
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GnomAD4 exome AF: 0.0000216 AC: 29AN: 1342240Hom.: 0 Cov.: 30 AF XY: 0.0000212 AC XY: 14AN XY: 661736
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GnomAD4 genome ? AF: 0.000204 AC: 31AN: 152090Hom.: 0 Cov.: 35 AF XY: 0.000215 AC XY: 16AN XY: 74372
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
RET-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 06, 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
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Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at