2-227293286-CCCTGGAAGT-CCCTGGAAGTCCTGGAAGT
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_000091.5(COL4A3):c.3321_3329dup(p.Ser1108_Gly1110dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,460 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
COL4A3
NM_000091.5 inframe_insertion
NM_000091.5 inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.16
Genes affected
COL4A3 (HGNC:2204): (collagen type IV alpha 3 chain) Type IV collagen, the major structural component of basement membranes, is a multimeric protein composed of 3 alpha subunits. These subunits are encoded by 6 different genes, alpha 1 through alpha 6, each of which can form a triple helix structure with 2 other subunits to form type IV collagen. This gene encodes alpha 3. In the Goodpasture syndrome, autoantibodies bind to the collagen molecules in the basement membranes of alveoli and glomeruli. The epitopes that elicit these autoantibodies are localized largely to the non-collagenous C-terminal domain of the protein. A specific kinase phosphorylates amino acids in this same C-terminal region and the expression of this kinase is upregulated during pathogenesis. This gene is also linked to an autosomal recessive form of Alport syndrome. The mutations contributing to this syndrome are also located within the exons that encode this C-terminal region. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jun 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000091.5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A3 | NM_000091.5 | c.3321_3329dup | p.Ser1108_Gly1110dup | inframe_insertion | 38/52 | ENST00000396578.8 | |
MFF-DT | NR_102371.1 | n.244-11498_244-11497insACTTCCAGG | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A3 | ENST00000396578.8 | c.3321_3329dup | p.Ser1108_Gly1110dup | inframe_insertion | 38/52 | 1 | NM_000091.5 | P1 | |
MFF-DT | ENST00000439598.6 | n.244-11498_244-11497insACTTCCAGG | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461460Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727044
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
Bravo
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ClinVar
Not reported inComputational scores
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at