rs104886376

Positions:

• chrX-108440126-ATG-A

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_033380.3(COL4A5):​c.2_3del​(p.Met1?) variant causes a frameshift, start lost change. Variant has been reported in Lovd as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 20)
• Consequence: COL4A5 NM_033380.3 frameshift, start_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04

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 Likely_pathogenic. Variant got 9 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 102 pathogenic variants in the truncated region.
• PP5: Variant X-108440126-ATG-A is Pathogenic according to our data. Variant chrX-108440126-ATG-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A5	NM_033380.3	c.2_3del	p.Met1?	frameshift_variant, start_lost	1/53	ENST00000328300.11	NP_203699.1
COL4A5	NM_000495.5	c.2_3del	p.Met1?	frameshift_variant, start_lost	1/51		NP_000486.1
COL4A5	XM_047441811.1	c.2_3del	p.Met1?	frameshift_variant, start_lost	1/42		XP_047297767.1
COL4A5	XM_047441810.1	c.-375_-374del		5_prime_UTR_variant	1/54		XP_047297766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A5	ENST00000328300.11	c.2_3del	p.Met1?	frameshift_variant, start_lost	1/53	1	NM_033380.3	ENSP00000331902

Frequencies

GnomAD3 genomes Cov.: 20

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

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs104886376; hg19: chrX-107683356;