rs104886369

Variant names:

• chrX-108622729-GGTA-G
• rs104886369
• NM_033380.3:c.2825_2827delGTA

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PM4_Supporting PP5

The NM_033380.3(COL4A5):​c.2825_2827delGTA​(p.Ser942del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in Lovd as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: COL4A5 NM_033380.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.89

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 6 ACMG points.

• PM1: In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_033380.3
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_033380.3. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant X-108622729-GGTA-G is Pathogenic according to our data. Variant chrX-108622729-GGTA-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A5	NM_033380.3	c.2825_2827delGTA	p.Ser942del	disruptive_inframe_deletion	Exon 33 of 53	ENST00000328300.11	NP_203699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A5	ENST00000328300.11	c.2825_2827delGTA	p.Ser942del	disruptive_inframe_deletion	Exon 33 of 53	1	NM_033380.3	ENSP00000331902.7
COL4A5	ENST00000483338.1	c.1649_1651delGTA	p.Ser550del	disruptive_inframe_deletion	Exon 17 of 20	1		ENSP00000495685.1
COL4A5	ENST00000361603.7	c.2825_2827delGTA	p.Ser942del	disruptive_inframe_deletion	Exon 33 of 51	2		ENSP00000354505.2
COL4A5	ENST00000505728.1	c.56_58delGTA	p.Ser19del	disruptive_inframe_deletion	Exon 1 of 5	3		ENSP00000424137.1

Frequencies

GnomAD3 genomes Cov.: 23

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

GnomAD4 genome Cov.: 23

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: rs104886369; hg19: chrX-107865959;