chr9-134834972-TCTC-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4_SupportingPP5_Moderate

The NM_000093.5(COL5A1):​c.5141_5143delCCT​(p.Ser1714del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

COL5A1
NM_000093.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.85
Variant links:
Genes affected
COL5A1 (HGNC:2209): (collagen type V alpha 1 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. The encoded procollagen protein occurs commonly as the heterotrimer pro-alpha1(V)-pro-alpha1(V)-pro-alpha2(V). Mutations in this gene are associated with Ehlers-Danlos syndrome, types I and II. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000093.5. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 9-134834972-TCTC-T is Pathogenic according to our data. Variant chr9-134834972-TCTC-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 409098.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL5A1NM_000093.5 linkc.5141_5143delCCT p.Ser1714del disruptive_inframe_deletion Exon 65 of 66 ENST00000371817.8 NP_000084.3 P20908-1A0A024R8E5B2ZZ86Q59EE7
COL5A1NM_001278074.1 linkc.5141_5143delCCT p.Ser1714del disruptive_inframe_deletion Exon 65 of 66 NP_001265003.1 B2ZZ86Q59EE7
LOC101448202NR_103451.2 linkn.71-14766_71-14764delGAG intron_variant Intron 1 of 1
COL5A1XM_017014266.3 linkc.*2220_*2222delCTC downstream_gene_variant XP_016869755.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL5A1ENST00000371817.8 linkc.5141_5143delCCT p.Ser1714del disruptive_inframe_deletion Exon 65 of 66 1 NM_000093.5 ENSP00000360882.3 P20908-1
COL5A1ENST00000371820.4 linkc.5141_5143delCCT p.Ser1714del disruptive_inframe_deletion Exon 65 of 66 2 ENSP00000360885.4 P20908-2H7BY82

Frequencies

GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Ehlers-Danlos syndrome, classic type, 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 07, 2016This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a COL5A1-related disease. In summary, this variant is a novel in-frame deletion with uncertain impact on protein function. Because it has been observed as arising de novo in an affected individual, it has been classified as Likely Pathogenic. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. Family studies have indicated that this variant was not present in the parents of an individual with classical Ehlers-Danlos syndrome, which suggests that it was de novo in that affected individual (Invitae). This sequence change deletes 3 nucleotides from exon 65 of the COL5A1 mRNA (c.5141_5143delCCT). This leads to the deletion of 1 amino acid residue in the COL5A1 protein (p.Ser1714del) but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1060502250; hg19: chr9-137726818; API