X-108655431-G-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_033380.3(COL4A5):c.3347G>T(p.Gly1116Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,687 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 Likely pathogenic (★★).
Frequency
Consequence
NM_033380.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.3347G>T | p.Gly1116Val | missense_variant | 37/53 | ENST00000328300.11 | NP_203699.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.3347G>T | p.Gly1116Val | missense_variant | 37/53 | 1 | NM_033380.3 | ENSP00000331902.7 | ||
COL4A5 | ENST00000361603.7 | c.3347G>T | p.Gly1116Val | missense_variant | 37/51 | 2 | ENSP00000354505.2 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1097687Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 363219
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
X-linked Alport syndrome Pathogenic:3
Likely pathogenic, criteria provided, single submitter | clinical testing | Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota | Dec 13, 2017 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 29, 2022 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Genomic Medicine Lab, University of California San Francisco | - | - - |
COL4A5-related disorder Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 13, 2023 | The COL4A5 c.3347G>T variant is predicted to result in the amino acid substitution p.Gly1116Val. This variant was reported in at least one individual presenting with microhematuria (Family 53, Table S1, Bekheirnia et al 2010. PubMed ID: 20378821). This variant has not been reported in a large population database, indicating this variant is rare. The p.Gly1116 residue resides in the triple-helical region (residues 42 – 1456) of the COL4A5 protein (uniprot.org). The majority of pathogenic variants in COL4A5 substitute a glycine residue to a bulkier amino acid in the triple-helical domain (Hudson et al. 1993. PubMed ID: 8253711; https://www.ncbi.nlm.nih.gov/books/NBK1207/). This variant is interpreted as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at