rs148687561
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP2PP3BP6BS2
The NM_000093.5(COL5A1):c.4522C>A(p.Pro1508Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000688 in 1,613,778 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1508L) has been classified as Benign.
Frequency
Consequence
NM_000093.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.4522C>A | p.Pro1508Thr | missense_variant | 58/66 | ENST00000371817.8 | |
LOC101448202 | NR_103451.2 | n.89G>T | non_coding_transcript_exon_variant | 2/2 | |||
COL5A1 | NM_001278074.1 | c.4522C>A | p.Pro1508Thr | missense_variant | 58/66 | ||
COL5A1 | XM_017014266.3 | c.4522C>A | p.Pro1508Thr | missense_variant | 58/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.4522C>A | p.Pro1508Thr | missense_variant | 58/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.4522C>A | p.Pro1508Thr | missense_variant | 58/66 | 2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251274Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135868
GnomAD4 exome AF: 0.0000725 AC: 106AN: 1461572Hom.: 0 Cov.: 34 AF XY: 0.0000729 AC XY: 53AN XY: 727104
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74358
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 08, 2023 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Occurs in the triple helical domain at the X position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the X position is not a common mechanism of disease (Symoens et al., 2012; HGMD); This variant is associated with the following publications: (PMID: 22696272) - |
Ehlers-Danlos syndrome, classic type, 1;C5543412:Fibromuscular dysplasia, multifocal Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 06, 2022 | - - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Sep 12, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at