20-3082796-C-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5
The NM_000490.5(AVP):c.329G>A(p.Cys110Tyr) 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C110S) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000490.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AVP | NM_000490.5 | c.329G>A | p.Cys110Tyr | missense_variant | 3/3 | ENST00000380293.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AVP | ENST00000380293.3 | c.329G>A | p.Cys110Tyr | missense_variant | 3/3 | 1 | NM_000490.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1094294Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 522670
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Diabetes insipidus Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | DASA | Mar 25, 2022 | The c.329G>A;p.(Cys110Tyr) missense change has been observed in affected individual(s) (PMID: 28008190)-PS4_supporting. The variant is located in a mutational hot spot and/or critical and well-established functional domain (Hormone_5) - PM1. This variant is not present in population databases (rs1057521601- gnomAD; ABraOM no frequency - http://abraom.ib.usp.br.) - PM2. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is likely pathogenic - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 25, 2016 | The C110Y variant in the AVP gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The C110Y variant was not observed in approximately 3,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The C110Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret C110Y as a variant of uncertain significance. - |
Neurohypophyseal diabetes insipidus Other:1
Uncertain risk allele, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | Potent mutations in AVP gene can lead to decreased production of Anti Diuretic hormone which leads to central Diabetes insipidus.This particular variant rs1057521601 can predispose Familial Neurohypophysial Diabetes Insipidus (FNDI) and strength of predisposition is yet to be studied - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at