rs104886168
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PS1_ModeratePM1PP3_StrongPP5
The NM_033380.3(COL4A5):c.2060G>A(p.Gly687Glu) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in Lovd as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
COL4A5
NM_033380.3 missense
NM_033380.3 missense
Scores
11
4
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 9.26
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PS1
?
Transcript NM_033380.3 (COL4A5) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
PM1
?
In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 3 uncertain in NM_033380.3
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.984
PP5
?
Variant X-108601903-G-A is Pathogenic according to our data. Variant chrX-108601903-G-A is described in Lovd as [Pathogenic]. Variant chrX-108601903-G-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.2060G>A | p.Gly687Glu | missense_variant | 27/53 | ENST00000328300.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.2060G>A | p.Gly687Glu | missense_variant | 27/53 | 1 | NM_033380.3 | ||
COL4A5 | ENST00000483338.1 | c.884G>A | p.Gly295Glu | missense_variant | 11/20 | 1 | |||
COL4A5 | ENST00000361603.7 | c.2060G>A | p.Gly687Glu | missense_variant | 27/51 | 2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1048451Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 331957
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1048451
Hom.:
Cov.:
25
AF XY:
AC XY:
0
AN XY:
331957
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H;.
MutationTaster
Benign
A;A
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.
REVEL
Pathogenic
Sift
Uncertain
D;D;.
Sift4G
Uncertain
D;D;.
Polyphen
1.0
.;D;D
Vest4
MutPred
Loss of catalytic residue at P683 (P = 0.0946);Loss of catalytic residue at P683 (P = 0.0946);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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