rs281874682
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_033380.3(COL4A5):c.1883C>A(p.Pro628Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/20 in silico tools predict 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 missense
NM_033380.3 missense
Scores
1
5
11
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.94
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
In a compositionally_biased_region Pro residues (size 22) in uniprot entity CO4A5_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_033380.3
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.1883C>A | p.Pro628Gln | missense_variant | 25/53 | ENST00000328300.11 | NP_203699.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.1883C>A | p.Pro628Gln | missense_variant | 25/53 | 1 | NM_033380.3 | ENSP00000331902.7 | ||
COL4A5 | ENST00000483338.1 | c.707C>A | p.Pro236Gln | missense_variant | 9/20 | 1 | ENSP00000495685.1 | |||
COL4A5 | ENST00000361603.7 | c.1883C>A | p.Pro628Gln | missense_variant | 25/51 | 2 | ENSP00000354505.2 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD3 exomes AF: 0.00000546 AC: 1AN: 183089Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67619
GnomAD3 exomes
AF:
AC:
1
AN:
183089
Hom.:
AF XY:
AC XY:
1
AN XY:
67619
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 23
GnomAD4 genome
Cov.:
23
ExAC
AF:
AC:
2
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
.;D;T
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;.
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;.
REVEL
Benign
Sift
Benign
T;T;.
Sift4G
Benign
T;T;.
Polyphen
0.10, 0.051
.;B;B
Vest4
MutPred
Loss of glycosylation at P628 (P = 0.0508);Loss of glycosylation at P628 (P = 0.0508);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at