rs1030105888
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2
The NM_000093.5(COL5A1):c.2842C>T(p.Arg948Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R948Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000093.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.2842C>T | p.Arg948Trp | missense_variant, splice_region_variant | 35/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.2842C>T | p.Arg948Trp | missense_variant, splice_region_variant | 35/66 | ||
COL5A1 | XM_017014266.3 | c.2842C>T | p.Arg948Trp | missense_variant, splice_region_variant | 35/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.2842C>T | p.Arg948Trp | missense_variant, splice_region_variant | 35/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.2842C>T | p.Arg948Trp | missense_variant, splice_region_variant | 35/66 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251330Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135898
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461736Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727162
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74366
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2017 | The p.R948W variant (also known as c.2842C>T), located in coding exon 35 of the COL5A1 gene, results from a C to T substitution at nucleotide position 2842. The arginine at codon 948 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration has been identified in a single individual in a cohort of patients with sporadic aortic dissection; however, clinical details were limited (Li Z et al. Sci China Life Sci, 2017 Jan;60:57-65). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Ehlers-Danlos syndrome, classic type, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 11, 2023 | Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 519646). This missense change has been observed in individual(s) with aortic dissection (PMID: 34041919). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 948 of the COL5A1 protein (p.Arg948Trp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at