chr20-3082703-G-A
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_000490.5(AVP):c.422C>T(p.Ala141Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000333 in 1,290,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A141T) has been classified as Uncertain significance.
Frequency
Consequence
NM_000490.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Our verdict: Likely_benign. The variant received -1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 151878Hom.: 0 Cov.: 34 show subpopulations
GnomAD2 exomes AF: 0.00 AC: 0AN: 10426 AF XY: 0.00
GnomAD4 exome AF: 0.0000176 AC: 20AN: 1138458Hom.: 0 Cov.: 32 AF XY: 0.0000146 AC XY: 8AN XY: 548608 show subpopulations
GnomAD4 genome AF: 0.000151 AC: 23AN: 151986Hom.: 0 Cov.: 34 AF XY: 0.000148 AC XY: 11AN XY: 74320 show subpopulations
ClinVar
Submissions by phenotype
Neurohypophyseal diabetes insipidus Uncertain:1
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not provided Uncertain:1
This variant has not been reported in the literature in individuals affected with AVP-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 141 of the AVP protein (p.Ala141Val). This variant is present in population databases (rs566930108, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at