rs104886087

Positions:

• chrX-108582917-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_033380.3(COL4A5):​c.970C>T​(p.Pro324Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in Lovd as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: COL4A5 NM_033380.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.68

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.859
• PP5: Variant X-108582917-C-T is Pathogenic according to our data. Variant chrX-108582917-C-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL4A5	NM_033380.3	c.970C>T	p.Pro324Ser	missense_variant	17/53	ENST00000328300.11	NP_203699.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL4A5	ENST00000328300.11	c.970C>T	p.Pro324Ser	missense_variant	17/53	1	NM_033380.3	ENSP00000331902.7
COL4A5	ENST00000483338	c.-207C>T		5_prime_UTR_variant	1/20	1		ENSP00000495685.1
COL4A5	ENST00000361603.7	c.970C>T	p.Pro324Ser	missense_variant	17/51	2		ENSP00000354505.2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.90	.;D
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Pathogenic	0.85	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Pathogenic	0.96	D
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.5	D;D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0040	D;D
Sift4G	Benign	0.24	T;T
Polyphen		1.0	.;D
Vest4		0.50
MutPred		0.54		Gain of phosphorylation at P324 (P = 0.0031);Gain of phosphorylation at P324 (P = 0.0031);
MVP		0.94
MPC		0.30
ClinPred		0.99	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.35

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: rs104886087; hg19: chrX-107826147;