chr9-134690995-C-T
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000371817.8(COL5A1):c.193C>T(p.Arg65Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,613,832 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R65Q) has been classified as Likely benign.
Frequency
Consequence
ENST00000371817.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.193C>T | p.Arg65Trp | missense_variant | 2/66 | ENST00000371817.8 | NP_000084.3 | |
COL5A1 | NM_001278074.1 | c.193C>T | p.Arg65Trp | missense_variant | 2/66 | NP_001265003.1 | ||
COL5A1 | XM_017014266.3 | c.193C>T | p.Arg65Trp | missense_variant | 2/65 | XP_016869755.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.193C>T | p.Arg65Trp | missense_variant | 2/66 | 1 | NM_000093.5 | ENSP00000360882 | P4 | |
COL5A1 | ENST00000371820.4 | c.193C>T | p.Arg65Trp | missense_variant | 2/66 | 2 | ENSP00000360885 | A2 | ||
COL5A1 | ENST00000464187.1 | n.379C>T | non_coding_transcript_exon_variant | 2/6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00141 AC: 214AN: 152270Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.00216 AC: 543AN: 251154Hom.: 3 AF XY: 0.00248 AC XY: 337AN XY: 135862
GnomAD4 exome AF: 0.00166 AC: 2419AN: 1461444Hom.: 12 Cov.: 32 AF XY: 0.00189 AC XY: 1372AN XY: 726998
GnomAD4 genome AF: 0.00141 AC: 215AN: 152388Hom.: 1 Cov.: 33 AF XY: 0.00154 AC XY: 115AN XY: 74524
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 16, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | COL5A1: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 13, 2020 | This variant is associated with the following publications: (PMID: 24036952, 28748566, 30858776, 31903434) - |
Ehlers-Danlos syndrome, classic type, 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 21, 2023 | - - |
Fibromuscular dysplasia, multifocal Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Mar 15, 2022 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 19, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Ehlers-Danlos syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Aug 16, 2021 | - - |
Ehlers-Danlos syndrome type 7A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at