rs772521985
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_000093.5(COL5A1):c.3292G>A(p.Ala1098Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,550,494 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign 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. A1098S) 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL5A1 | NM_000093.5 | c.3292G>A | p.Ala1098Thr | missense_variant | 42/66 | ENST00000371817.8 | |
COL5A1 | NM_001278074.1 | c.3292G>A | p.Ala1098Thr | missense_variant | 42/66 | ||
COL5A1 | XM_017014266.3 | c.3292G>A | p.Ala1098Thr | missense_variant | 42/65 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL5A1 | ENST00000371817.8 | c.3292G>A | p.Ala1098Thr | missense_variant | 42/66 | 1 | NM_000093.5 | P4 | |
COL5A1 | ENST00000371820.4 | c.3292G>A | p.Ala1098Thr | missense_variant | 42/66 | 2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000572 AC: 87AN: 152090Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000129 AC: 20AN: 155288Hom.: 0 AF XY: 0.000110 AC XY: 9AN XY: 81862
GnomAD4 exome AF: 0.0000758 AC: 106AN: 1398404Hom.: 1 Cov.: 31 AF XY: 0.0000638 AC XY: 44AN XY: 689752
GnomAD4 genome ? AF: 0.000572 AC: 87AN: 152090Hom.: 0 Cov.: 33 AF XY: 0.000512 AC XY: 38AN XY: 74280
ClinVar
Submissions by phenotype
Ehlers-Danlos syndrome, classic type Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Apr 06, 2020 | COL5A1 NM_000093.4 exon 42 p.Ala1098Thr (c.3292G>A): This variant has not been reported in the literature but is present in 0.1% (29/17386) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/9-137698068-G-A). This variant is present in ClinVar (Variation ID:212960). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Ehlers-Danlos syndrome, classic type, 1 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 20, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Dec 08, 2020 | COL5A1 NM_000093.4 exon 42 p.Ala1098Thr (c.3292G>A): This variant has not been reported in the literature but is present in 0.1% (29/17386) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/9-137698068-G-A). This variant is present in ClinVar (Variation ID:212960). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Ehlers-Danlos syndrome, classic type, 1;C5543412:Fibromuscular dysplasia, multifocal Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | COL5A1 NM_000093.4 exon 42 p.Ala1098Thr (c.3292G>A): This variant has not been reported in the literature but is present in 0.1% (29/17386) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/9-137698068-G-A). This variant is present in ClinVar (Variation ID:212960). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Connective tissue disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Jun 01, 2018 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 11, 2020 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at