rs281874705

chrX-108622690-C-T

Variant summary

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

The NM_033380.3(COL4A5):c.2782C>T(p.Gln928Ter) variant causes a stop gained change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in Lovd as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: COL4A5 NM_033380.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.96

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 undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant X-108622690-C-T is Pathogenic according to our data. Variant chrX-108622690-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL4A5	NM_033380.3	c.2782C>T	p.Gln928Ter	stop_gained	33/53	ENST00000328300.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL4A5	ENST00000328300.11	c.2782C>T	p.Gln928Ter	stop_gained	33/53	1	NM_033380.3
COL4A5	ENST00000483338.1	c.1606C>T	p.Gln536Ter	stop_gained	17/20	1
COL4A5	ENST00000361603.7	c.2782C>T	p.Gln928Ter	stop_gained	33/51	2		P1
COL4A5	ENST00000505728.1	c.16C>T	p.Gln6Ter	stop_gained	1/5	3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1097315 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 362871

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.74	D
BayesDel_noAF	Pathogenic	0.66
Cadd	Pathogenic	37
Dann	Uncertain	1.0
FATHMM_MKL	Pathogenic	0.99	D
MutationTaster	Benign	1.0	A;A
Vest4		0.92
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs281874705; hg19: chrX-107865920;