rs104886342

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_033380.3(COL4A5):​c.2062_2114dup​(p.Ile706AsnfsTer48) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 23)

Consequence

COL4A5
NM_033380.3 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.26
Variant links:
Genes affected
COL4A5 (HGNC:2207): (collagen type IV alpha 5 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. Mutations in this gene are associated with X-linked Alport syndrome, also known as hereditary nephritis. 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. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Aug 2010]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL4A5NM_033380.3 linkuse as main transcriptc.2062_2114dup p.Ile706AsnfsTer48 frameshift_variant 27/53 ENST00000328300.11 NP_203699.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL4A5ENST00000328300.11 linkuse as main transcriptc.2062_2114dup p.Ile706AsnfsTer48 frameshift_variant 27/531 NM_033380.3 ENSP00000331902 P29400-2
COL4A5ENST00000483338.1 linkuse as main transcriptc.886_938dup p.Ile314AsnfsTer48 frameshift_variant 11/201 ENSP00000495685
COL4A5ENST00000361603.7 linkuse as main transcriptc.2062_2114dup p.Ile706AsnfsTer48 frameshift_variant 27/512 ENSP00000354505 P1P29400-1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
25
GnomAD4 genome
Cov.:
23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs104886342; hg19: chrX-107845132; API