rs104886267
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3PP5
The NM_033380.3(COL4A5):c.4087G>A(p.Gly1363Ser) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000898 in 111,403 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. 13/21 in silico tools predict a damaging outcome for this variant. 2/2 splice prediction tools predicting alterations to normal splicing. Variant has been reported in Lovd as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1363A) 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 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.4087G>A | p.Gly1363Ser | missense_variant, splice_region_variant | 46/53 | ENST00000328300.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.4087G>A | p.Gly1363Ser | missense_variant, splice_region_variant | 46/53 | 1 | NM_033380.3 | ||
COL4A5 | ENST00000361603.7 | c.4069G>A | p.Gly1357Ser | missense_variant, splice_region_variant | 44/51 | 2 | P1 | ||
COL4A5 | ENST00000489230.1 | n.490G>A | splice_region_variant, non_coding_transcript_exon_variant | 5/8 | 5 | ||||
COL4A5 | ENST00000510690.2 | n.581G>A | splice_region_variant, non_coding_transcript_exon_variant | 4/11 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000898 AC: 1AN: 111403Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33587
GnomAD4 exome Cov.: 29
GnomAD4 genome ? AF: 0.00000898 AC: 1AN: 111403Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33587
ClinVar
Not reported inComputational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at