rs104886330

Positions:

• chrX-108595568-CAACCTGGTTTGCCAGGTCTCCCAGGTCCTCCAGGTAA-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_033380.3(COL4A5):​c.1485_1516+5del variant causes a splice donor, splice donor region, coding sequence, intron 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.

• Frequency: Genomes: not found (cov: 22)
• Consequence: COL4A5 NM_033380.3 splice_donor, splice_donor_region, coding_sequence, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.00

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.018124508 fraction of the gene. Cryptic splice site detected, with MaxEntScore 5.4, offset of -20, new splice context is: aggGTaacc. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A5	NM_033380.3	c.1485_1516+5del		splice_donor_variant, splice_donor_region_variant, coding_sequence_variant, intron_variant	22/53	ENST00000328300.11	NP_203699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A5	ENST00000328300.11	c.1485_1516+5del		splice_donor_variant, splice_donor_region_variant, coding_sequence_variant, intron_variant	22/53	1	NM_033380.3	ENSP00000331902
COL4A5	ENST00000483338.1	c.309_340+5del		splice_donor_variant, splice_donor_region_variant, coding_sequence_variant, intron_variant	6/20	1		ENSP00000495685
COL4A5	ENST00000361603.7	c.1485_1516+5del		splice_donor_variant, splice_donor_region_variant, coding_sequence_variant, intron_variant	22/51	2		ENSP00000354505	P1

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs104886330; hg19: chrX-107838798;