rs104886059
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_033380.3(COL4A5):c.548G>A(p.Gly183Asp) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G183S) has been classified as Likely pathogenic.
Frequency
Consequence
NM_033380.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.548G>A | p.Gly183Asp | missense_variant, splice_region_variant | 10/53 | ENST00000328300.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.548G>A | p.Gly183Asp | missense_variant, splice_region_variant | 10/53 | 1 | NM_033380.3 | ||
COL4A5 | ENST00000361603.7 | c.548G>A | p.Gly183Asp | missense_variant, splice_region_variant | 10/51 | 2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1056135Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 330501
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
X-linked Alport syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | 3billion | May 22, 2022 | The variant is not observed in the gnomAD v2.1.1 dataset. It is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.97; 3Cnet: 0.95). Different missense changes at the same codon (p.Gly183Ser, p.Gly183Val) have been reported to be associated with COL4A5 related disorder (ClinVar ID: VCV000438706 / PMID: 15954103). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.