X-108573557-T-G

Variant names:

• chrX-108573557-T-G
• rs104886415
• NM_033380.3:c.466-17T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033380.3(COL4A5):​c.466-17T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: COL4A5 NM_033380.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 1 publications found

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]

COL4A5 Gene-Disease associations (from GenCC):

• Alport syndrome

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen, G2P
• X-linked Alport syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Genomics England PanelApp, Myriad Women’s Health, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL4A5	NM_033380.3	c.466-17T>G		intron_variant	Intron 8 of 52	ENST00000328300.11	NP_203699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL4A5	ENST00000328300.11	c.466-17T>G		intron_variant	Intron 8 of 52	1	NM_033380.3	ENSP00000331902.7
COL4A5	ENST00000361603.7	c.466-17T>G		intron_variant	Intron 8 of 50	2		ENSP00000354505.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 23

Alfa AF: 0.000116 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.025
DANN	Benign	0.68
PhyloP100		-0.068

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		3.0
SpliceAI score (max)		0.50		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.50		Position offset: 17

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

Other links and lift over

dbSNP: rs104886415; hg19: chrX-107816787;