rs747041833
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_033380.3(COL4A5):āc.4726C>Gā(p.Pro1576Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,206,466 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1576S) has been classified as Likely benign.
Frequency
Consequence
NM_033380.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.4726C>G | p.Pro1576Ala | missense_variant | 51/53 | ENST00000328300.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.4726C>G | p.Pro1576Ala | missense_variant | 51/53 | 1 | NM_033380.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000897 AC: 1AN: 111432Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33636
GnomAD3 exomes AF: 0.00000546 AC: 1AN: 183041Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67637
GnomAD4 exome AF: 0.00000183 AC: 2AN: 1095034Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 360540
GnomAD4 genome ? AF: 0.00000897 AC: 1AN: 111432Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33636
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 06, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | This sequence change replaces proline with alanine at codon 1570 of the COL4A5 protein (p.Pro1570Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine. This variant is not present in population databases (ExAC 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: 585547). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 14, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at