rs397515496
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PM5PP3_ModeratePP5
The NM_033380.3(COL4A5):c.2678G>C(p.Gly893Ala) 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 predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G893D) 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 Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.2678G>C | p.Gly893Ala | missense_variant, splice_region_variant | 32/53 | ENST00000328300.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.2678G>C | p.Gly893Ala | missense_variant, splice_region_variant | 32/53 | 1 | NM_033380.3 | ||
COL4A5 | ENST00000483338.1 | c.1502G>C | p.Gly501Ala | missense_variant, splice_region_variant | 16/20 | 1 | |||
COL4A5 | ENST00000361603.7 | c.2678G>C | p.Gly893Ala | missense_variant, splice_region_variant | 32/51 | 2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD4 exome Cov.: 27
GnomAD4 genome Cov.: 22
ClinVar
Submissions by phenotype
Alport syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Sydney Genome Diagnostics, Children's Hospital Westmead | Oct 24, 2018 | This patient is hemizygous for the c.2678G>C p.(Gly893Ala) variant in exon 32 of the COL4A5 gene. To our knowledge, this variant has not been previously reported. However, other variants involving the same same amino acid change, c.2677G>C p.(Gly893Arg) and c.2678G>T p.(Gly893Val), have been previously reported in patients with Alport syndrome in the ALPORT database (see http://www.arup.utah.edu/database/alport/alport_welcome.php). It is assumed that this variant is pathogenic as it results in substitution of one of the invariant glycine residues in the triple helical domain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at