rs768003309
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PM1PM2PM5PP3_StrongPP5_Very_Strong
The NM_000092.5(COL4A4):c.2374G>A(p.Gly792Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. G792E) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000092.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A4 | NM_000092.5 | c.2374G>A | p.Gly792Arg | missense_variant | 28/48 | ENST00000396625.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A4 | ENST00000396625.5 | c.2374G>A | p.Gly792Arg | missense_variant | 28/48 | 5 | NM_000092.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249562Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135398
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461778Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727194
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Autosomal recessive Alport syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jan 31, 2018 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 12, 2023 | This missense change has been observed in individual(s) with Alport syndrome (PMID: 16338941). It has also been observed to segregate with disease in related individuals. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL4A4 protein function. ClinVar contains an entry for this variant (Variation ID: 556413). This variant is present in population databases (rs768003309, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 792 of the COL4A4 protein (p.Gly792Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at