rs150487609
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_000093.5(COL5A1):c.3110C>T(p.Thr1037Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000901 in 1,598,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T1037T) 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.3110C>T | p.Thr1037Met | missense_variant | 39/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.3110C>T | p.Thr1037Met | missense_variant | 39/66 | ||
COL5A1 | XM_017014266.3 | c.3110C>T | p.Thr1037Met | missense_variant | 39/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.3110C>T | p.Thr1037Met | missense_variant | 39/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.3110C>T | p.Thr1037Met | missense_variant | 39/66 | 2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000783 AC: 17AN: 217014Hom.: 0 AF XY: 0.0000683 AC XY: 8AN XY: 117182
GnomAD4 exome AF: 0.0000913 AC: 132AN: 1446344Hom.: 0 Cov.: 31 AF XY: 0.0000905 AC XY: 65AN XY: 717978
GnomAD4 genome AF: 0.0000788 AC: 12AN: 152318Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6AN XY: 74486
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 03, 2017 | The p.T1037M variant (also known as c.3110C>T), located in coding exon 39 of the COL5A1 gene, results from a C to T substitution at nucleotide position 3110. The threonine at codon 1037 is replaced by methionine, an amino acid with similar properties. This amino acid position is not well 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 13, 2023 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter 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 (HGMD, PMID: 22696272); 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 | Sep 03, 2021 | - - |
Ehlers-Danlos syndrome, classic type, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at