chr2-27054035-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_021831.6(AGBL5):c.527C>T(p.Pro176Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 1,613,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_021831.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000171 AC: 43AN: 250892Hom.: 0 AF XY: 0.000170 AC XY: 23AN XY: 135578
GnomAD4 exome AF: 0.000255 AC: 373AN: 1461430Hom.: 0 Cov.: 31 AF XY: 0.000231 AC XY: 168AN XY: 726996
GnomAD4 genome AF: 0.000151 AC: 23AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74480
ClinVar
Submissions by phenotype
not provided Uncertain:2
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 176 of the AGBL5 protein (p.Pro176Leu). This variant is present in population databases (rs142859717, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with AGBL5-related conditions. ClinVar contains an entry for this variant (Variation ID: 871081). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. -
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Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at