rs104886079
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PP3_StrongPP5_Very_Strong
The NM_033380.3(COL4A5):c.884G>A(p.Gly295Asp) variant causes a missense 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. Variant has been reported in ClinVar as Pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G295S) has been classified as Uncertain significance.
Frequency
Consequence
NM_033380.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.884G>A | p.Gly295Asp | missense_variant | 15/53 | ENST00000328300.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.884G>A | p.Gly295Asp | missense_variant | 15/53 | 1 | NM_033380.3 | ||
COL4A5 | ENST00000361603.7 | c.884G>A | p.Gly295Asp | missense_variant | 15/51 | 2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
X-linked Alport syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 28, 2022 | - - |
Likely pathogenic, no assertion criteria provided | clinical testing | Counsyl | Sep 20, 2017 | - - |
Alport syndrome Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Sydney Genome Diagnostics, Children's Hospital Westmead | Sep 15, 2017 | This individual is hemizygous for a variant, c.884G>A p.(Gly295Asp), in the COL4A5 gene. The c.884G>A variant has not been reported in any population databases (i.e. ExAC, ESP or dbSNP).It has been previously described in an affected male individual with Alport Syndrome (Barker et al Am J Med Genet 2001 15;98(2):148-160). This variant results in the substitution of one of the invariant glycine residues within the triple helical domain. In silico analysis of pathogenicity (through Alamut Visual v2.8.1) using PolyPhen2, SIFT and MutationTaster suggested that this variant is pathogenic. This variant is considered to be a likely pathogenic according to the ACMG guidelines. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 17, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at