X-108597387-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_033380.3(COL4A5):​c.1598G>T​(p.Gly533Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000913 in 109,519 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000091 ( 0 hom., 0 hem., cov: 21)

Consequence

COL4A5
NM_033380.3 missense

Scores

15
1
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.91
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.983

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL4A5NM_033380.3 linkc.1598G>T p.Gly533Val missense_variant Exon 24 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.1598G>T p.Gly533Val missense_variant Exon 24 of 53 1 NM_033380.3 ENSP00000331902.7 P29400-2
COL4A5ENST00000483338.1 linkc.422G>T p.Gly141Val missense_variant Exon 8 of 20 1 ENSP00000495685.1 Q49AM6
COL4A5ENST00000361603.7 linkc.1598G>T p.Gly533Val missense_variant Exon 24 of 51 2 ENSP00000354505.2 P29400-1

Frequencies

GnomAD3 genomes
AF:
0.00000913
AC:
1
AN:
109519
Hom.:
0
Cov.:
21
AF XY:
0.00
AC XY:
0
AN XY:
31907
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000190
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000913
AC:
1
AN:
109519
Hom.:
0
Cov.:
21
AF XY:
0.00
AC XY:
0
AN XY:
31907
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000190
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.74
BayesDel_addAF
Pathogenic
0.74
D
BayesDel_noAF
Pathogenic
0.83
CADD
Uncertain
26
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.94
.;D;D
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.98
D;D;D
M_CAP
Pathogenic
0.97
D
MetaRNN
Pathogenic
0.98
D;D;D
MetaSVM
Pathogenic
0.92
D
MutationAssessor
Pathogenic
4.0
H;H;.
PrimateAI
Pathogenic
0.80
T
PROVEAN
Pathogenic
-8.1
D;D;.
REVEL
Pathogenic
0.95
Sift
Pathogenic
0.0
D;D;.
Sift4G
Pathogenic
0.0
D;D;.
Polyphen
1.0
.;D;D
Vest4
0.99
MutPred
0.83
Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);.;
MVP
1.0
MPC
0.37
ClinPred
1.0
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
1.0
gMVP
1.0

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

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

Other links and lift over

dbSNP: rs281874672; hg19: chrX-107840617; API