COL4A5 p.Gly201Ala
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is . The variant received 11 ACMG points: 11P and 0B. PM1PM2PM5PP2PP3_Strong
Pathogenic
The NM_033380.3(COL4A5):c.602G>C(p.Gly201Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000945 in 1,057,742 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G201R) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 9.5e-7 ( 0 hom. 1 hem. )
Consequence
COL4A5
NM_033380.3 missense
NM_033380.3 missense
Scores
13
4
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.92
Publications
1 publications found
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]
COL4A5 Gene-Disease associations (from GenCC):
- Alport syndromeInheritance: XL Classification: DEFINITIVE Submitted by: G2P, ClinGen
- X-linked Alport syndromeInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Myriad Women's Health, Labcorp Genetics (formerly Invitae)
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new If you want to explore the variant's impact on the transcript NM_033380.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PM1
In a hotspot region, there are 9 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 9 uncertain in NM_033380.3
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chrX-108575965-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 1392961.Status of the report is criteria_provided_single_submitter, 1 stars.
PP2
Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 538 curated pathogenic missense variants (we use a threshold of 10). The gene has 138 curated benign missense variants. Gene score misZ: 2.4995 (below the threshold of 3.09). Trascript score misZ: NaN (below the threshold of 3.09). GenCC associations: The gene is linked to X-linked Alport syndrome, Alport syndrome.
PP3
REVEL computational evidence supports a deleterious effect, 0.99
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_033380.3. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| COL4A5 | TSL:1 MANE Select | c.602G>C | p.Gly201Ala | missense | Exon 10 of 53 | ENSP00000331902.7 | P29400-2 | ||
| COL4A5 | c.602G>C | p.Gly201Ala | missense | Exon 10 of 51 | ENSP00000619202.1 | ||||
| COL4A5 | TSL:2 | c.602G>C | p.Gly201Ala | missense | Exon 10 of 51 | ENSP00000354505.2 | P29400-1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
22
GnomAD2 exomes AF: 0.00000592 AC: 1AN: 168800 AF XY: 0.0000178 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
168800
AF XY:
Gnomad AFR exome
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Gnomad ASJ exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 9.45e-7 AC: 1AN: 1057742Hom.: 0 Cov.: 24 AF XY: 0.00000304 AC XY: 1AN XY: 328738 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1057742
Hom.:
Cov.:
24
AF XY:
AC XY:
1
AN XY:
328738
show subpopulations
African (AFR)
AF:
AC:
0
AN:
25669
American (AMR)
AF:
AC:
0
AN:
34866
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19039
East Asian (EAS)
AF:
AC:
0
AN:
29781
South Asian (SAS)
AF:
AC:
0
AN:
52109
European-Finnish (FIN)
AF:
AC:
0
AN:
40076
Middle Eastern (MID)
AF:
AC:
0
AN:
4052
European-Non Finnish (NFE)
AF:
AC:
0
AN:
807490
Other (OTH)
AF:
AC:
1
AN:
44660
GnomAD4 genome
GnomAD4 genome
Cov.:
22
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Pathogenic
D
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
MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.
Publications
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Other links and lift over
dbSNP: rs104886062 ;
hg19: chrX-107819195;