rs121434543
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong
The NM_001793.6(CDH3):āc.965A>Gā(p.Asn322Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N322I) has been classified as Pathogenic.
Frequency
Consequence
NM_001793.6 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 | UniProt |
---|---|---|---|---|---|---|---|
CDH3 | NM_001793.6 | c.965A>G | p.Asn322Ser | missense_variant | 8/16 | ENST00000264012.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH3 | ENST00000264012.9 | c.965A>G | p.Asn322Ser | missense_variant | 8/16 | 1 | NM_001793.6 | P1 | |
CDH3 | ENST00000429102.6 | c.965A>G | p.Asn322Ser | missense_variant | 8/16 | 1 | |||
CDH3 | ENST00000542274.5 | c.*703A>G | 3_prime_UTR_variant, NMD_transcript_variant | 7/15 | 2 | ||||
CDH3 | ENST00000569036.2 | c.*262A>G | 3_prime_UTR_variant, NMD_transcript_variant | 4/5 | 4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251174Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135768
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461766Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727176
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74334
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 04, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals affected with CDH3-related conditions. This variant is present in population databases (rs121434543, gnomAD 0.01%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 322 of the CDH3 protein (p.Asn322Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at