16-68808473-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004360.5(CDH1):c.437C>T(p.Ser146Phe) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_004360.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH1 | NM_004360.5 | c.437C>T | p.Ser146Phe | missense_variant | 4/16 | ENST00000261769.10 | NP_004351.1 | |
CDH1 | NM_001317184.2 | c.437C>T | p.Ser146Phe | missense_variant | 4/15 | NP_001304113.1 | ||
CDH1 | NM_001317185.2 | c.-1179C>T | 5_prime_UTR_variant | 4/16 | NP_001304114.1 | |||
CDH1 | NM_001317186.2 | c.-1383C>T | 5_prime_UTR_variant | 4/15 | NP_001304115.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary diffuse gastric adenocarcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto | Aug 01, 2022 | PM2 (PMID: 30311375) - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 03, 2024 | The p.S146F variant (also known as c.437C>T), located in coding exon 4 of the CDH1 gene, results from a C to T substitution at nucleotide position 437. The serine at codon 146 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This variant has been reported in an individual with a personal history of breast cancer diagnosed in Belgium (Garcia-Pelaez J et al. Lancet Oncol, 2023 Jan;24:91-106). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant 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.