rs376465385
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PS1_ModeratePM2PP3_Strong
The NM_020975.6(RET):c.1182C>G(p.Asn394Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.
Frequency
Consequence
NM_020975.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RET | NM_020975.6 | c.1182C>G | p.Asn394Lys | missense_variant | 6/20 | ENST00000355710.8 | NP_066124.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RET | ENST00000355710.8 | c.1182C>G | p.Asn394Lys | missense_variant | 6/20 | 5 | NM_020975.6 | ENSP00000347942 | P4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 12, 2022 | The p.N394K variant (also known as c.1182C>G), located in coding exon 6 of the RET gene, results from a C to G substitution at nucleotide position 1182. The asparagine at codon 394 is replaced by lysine, an amino acid with similar properties. This alteration was identified in an individual with Hirschsprung disease (Bolk S et al. Proc Natl Acad Sci U S A, 2000 Jan;97:268-73). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.