X-108440157-G-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_033380.3(COL4A5):c.32G>T(p.Gly11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,205,867 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 47 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000083 ( 0 hom., 3 hem., cov: 21)
Exomes 𝑓: 0.00013 ( 0 hom. 44 hem. )
Consequence
COL4A5
NM_033380.3 missense
NM_033380.3 missense
Scores
1
5
11
Clinical Significance
Conservation
PhyloP100: 2.69
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_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.38764292).
BS2
High Hemizygotes in GnomAd4 at 3 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
COL4A5 | NM_033380.3 | c.32G>T | p.Gly11Val | missense_variant | 1/53 | ENST00000328300.11 | NP_203699.1 | |
COL4A5 | NM_000495.5 | c.32G>T | p.Gly11Val | missense_variant | 1/51 | NP_000486.1 | ||
COL4A5 | XM_047441811.1 | c.32G>T | p.Gly11Val | missense_variant | 1/42 | XP_047297767.1 | ||
COL4A5 | XM_047441810.1 | c.-345G>T | 5_prime_UTR_variant | 1/54 | XP_047297766.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
COL4A5 | ENST00000328300.11 | c.32G>T | p.Gly11Val | missense_variant | 1/53 | 1 | NM_033380.3 | ENSP00000331902 |
Frequencies
GnomAD3 genomes AF: 0.0000826 AC: 9AN: 108996Hom.: 0 Cov.: 21 AF XY: 0.0000959 AC XY: 3AN XY: 31270
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GnomAD3 exomes AF: 0.0000771 AC: 14AN: 181467Hom.: 0 AF XY: 0.0000604 AC XY: 4AN XY: 66201
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GnomAD4 exome AF: 0.000129 AC: 142AN: 1096871Hom.: 0 Cov.: 29 AF XY: 0.000121 AC XY: 44AN XY: 362303
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GnomAD4 genome AF: 0.0000826 AC: 9AN: 108996Hom.: 0 Cov.: 21 AF XY: 0.0000959 AC XY: 3AN XY: 31270
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 24, 2023 | The c.32G>T (p.G11V) alteration is located in exon 1 (coding exon 1) of the COL4A5 gene. This alteration results from a G to T substitution at nucleotide position 32, causing the glycine (G) at amino acid position 11 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
0.80
.;P
Vest4
MutPred
Loss of MoRF binding (P = 0.1336);Loss of MoRF binding (P = 0.1336);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at