rs781230603
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2
The NM_000093.5(COL5A1):c.5338C>T(p.Pro1780Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,678 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P1780H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000093.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.5338C>T | p.Pro1780Ser | missense_variant | 65/66 | ENST00000371817.8 | |
LOC101448202 | NR_103451.2 | n.71-14963G>A | intron_variant, non_coding_transcript_variant | ||||
COL5A1 | NM_001278074.1 | c.5338C>T | p.Pro1780Ser | missense_variant | 65/66 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.5338C>T | p.Pro1780Ser | missense_variant | 65/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.5338C>T | p.Pro1780Ser | missense_variant | 65/66 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250620Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135646
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461432Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 727042
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152246Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74374
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 09, 2018 | The P1780S variant in the COL5A1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is observed in 7/33,580 alleles (0.02%) from individuals of Latino background, and 8/245,584 global alleles (0.003%), in large population cohorts (Lek et al., 2016). The P1780S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret P1780S as a variant of uncertain significance. - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 23, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at