rs281874712

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_033380.3(COL4A5):​c.3206G>A​(p.Gly1069Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,097,755 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

COL4A5
NM_033380.3 missense

Scores

11
5
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.07
Variant links:
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 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.885
PP5
Variant X-108626309-G-A is Pathogenic according to our data. Variant chrX-108626309-G-A is described in Lovd as [Likely_pathogenic]. Variant chrX-108626309-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL4A5NM_033380.3 linkc.3206G>A p.Gly1069Asp missense_variant Exon 36 of 53 ENST00000328300.11 NP_203699.1 P29400-2Q49AM6A7MBN3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL4A5ENST00000328300.11 linkc.3206G>A p.Gly1069Asp missense_variant Exon 36 of 53 1 NM_033380.3 ENSP00000331902.7 P29400-2
COL4A5ENST00000483338.1 linkc.2030G>A p.Gly677Asp missense_variant Exon 20 of 20 1 ENSP00000495685.1 Q49AM6
COL4A5ENST00000361603.7 linkc.3206G>A p.Gly1069Asp missense_variant Exon 36 of 51 2 ENSP00000354505.2 P29400-1
COL4A5ENST00000505728.1 linkc.437G>A p.Gly146Asp missense_variant Exon 4 of 5 3 ENSP00000424137.1 H0Y9H0

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
9.11e-7
AC:
1
AN:
1097755
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
363255
show subpopulations
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:
0.0000217
GnomAD4 genome
Cov.:
22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.53
BayesDel_addAF
Pathogenic
0.69
D
BayesDel_noAF
Pathogenic
0.75
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.92
.;D;T
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Pathogenic
0.92
D
MetaRNN
Pathogenic
0.88
D;D;D
MetaSVM
Uncertain
0.43
D
MutationAssessor
Pathogenic
3.9
H;H;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-4.6
D;D;.
REVEL
Pathogenic
0.88
Sift
Pathogenic
0.0
D;D;.
Sift4G
Uncertain
0.0020
D;D;.
Polyphen
1.0
.;D;D
Vest4
0.93
MutPred
0.53
Loss of glycosylation at S1071 (P = 0.1402);Loss of glycosylation at S1071 (P = 0.1402);.;
MVP
1.0
MPC
0.39
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.99
gMVP
1.0

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs281874712; hg19: chrX-107869539; API