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GeneBe

rs397509375

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_000090.4(COL3A1):c.582+6T>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

COL3A1
NM_000090.4 splice_donor_region, intron

Scores

1
1
Splicing: ADA: 0.9956
1
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.51
Variant links:
Genes affected
COL3A1 (HGNC:2201): (collagen type III alpha 1 chain) This gene encodes the pro-alpha1 chains of type III collagen, a fibrillar collagen that is found in extensible connective tissues such as skin, lung, uterus, intestine and the vascular system, frequently in association with type I collagen. Mutations in this gene are associated with Ehlers-Danlos syndrome type IV, and with aortic and arterial aneurysms. [provided by R. Dalgleish, Feb 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-188988140-T-A is Pathogenic according to our data. Variant chr2-188988140-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 101260.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COL3A1NM_000090.4 linkuse as main transcriptc.582+6T>A splice_donor_region_variant, intron_variant ENST00000304636.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COL3A1ENST00000304636.9 linkuse as main transcriptc.582+6T>A splice_donor_region_variant, intron_variant 1 NM_000090.4 P1P02461-1
COL3A1ENST00000450867.2 linkuse as main transcriptc.582+6T>A splice_donor_region_variant, intron_variant 1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Ehlers-Danlos syndrome, type 4 Pathogenic:1
Pathogenic, no assertion criteria providedclinical testingCollagen Diagnostic Laboratory, University of Washington-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.13
Cadd
Benign
15
Dann
Uncertain
0.98

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Benign
0.67
SpliceAI score (max)
0.93
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.93
Position offset: -6

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: rs397509375; hg19: chr2-189852866; API