rs982188184
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM1PP3BS2
The NM_033380.3(COL4A5):c.4898C>T(p.Ala1633Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,209,553 control chromosomes in the GnomAD database, including 1 homozygotes. There are 5 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_033380.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000717 AC: 8AN: 111647Hom.: 1 Cov.: 22 AF XY: 0.0000296 AC XY: 1AN XY: 33813
GnomAD4 exome AF: 0.00000911 AC: 10AN: 1097906Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 4AN XY: 363294
GnomAD4 genome AF: 0.0000717 AC: 8AN: 111647Hom.: 1 Cov.: 22 AF XY: 0.0000296 AC XY: 1AN XY: 33813
ClinVar
Submissions by phenotype
not provided Uncertain:2
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This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1627 of the COL4A5 protein (p.Ala1627Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL4A5-related conditions. ClinVar contains an entry for this variant (Variation ID: 591064). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt COL4A5 protein function with a negative predictive value of 95%. 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. -
X-linked Alport syndrome Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at