9-134824654-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2PP3_ModerateBS2
The NM_000093.5(COL5A1):c.4753C>T(p.Arg1585Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,614,180 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. R1585Q) has been classified as Likely benign.
Frequency
Consequence
NM_000093.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.4753C>T | p.Arg1585Trp | missense_variant | 62/66 | ENST00000371817.8 | |
LOC101448202 | NR_103451.2 | n.71-4445G>A | intron_variant, non_coding_transcript_variant | ||||
COL5A1 | NM_001278074.1 | c.4753C>T | p.Arg1585Trp | missense_variant | 62/66 | ||
COL5A1 | XM_017014266.3 | c.4753C>T | p.Arg1585Trp | missense_variant | 62/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.4753C>T | p.Arg1585Trp | missense_variant | 62/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.4753C>T | p.Arg1585Trp | missense_variant | 62/66 | 2 | A2 | ||
COL5A1 | ENST00000460264.5 | n.221C>T | non_coding_transcript_exon_variant | 3/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000399 AC: 10AN: 250668Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135604
GnomAD4 exome AF: 0.0000472 AC: 69AN: 1461856Hom.: 0 Cov.: 32 AF XY: 0.0000468 AC XY: 34AN XY: 727228
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74482
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 04, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 13, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Not located in the triple helical region, where the majority of pathogenic missense variants occur (Symoens et al., 2012; Stenson et al., 2014) - |
Ehlers-Danlos syndrome, classic type Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 15, 2018 | The COL5A1 c.4753C>T; p.Arg1585Trp variant (rs546865410), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 212988). This variant is found in the general population with an overall allele frequency of 0.004% (11/282004 alleles) in the Genome Aggregation Database. The arginine at codon 1585 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information, the clinical significance of the p.Arg1585Trp variant is uncertain at this time. - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 19, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at