chrX-108440180-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033380.3(COL4A5):​c.55C>G​(p.Leu19Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 21)

Consequence

COL4A5
NM_033380.3 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15220559).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL4A5NM_033380.3 linkuse as main transcriptc.55C>G p.Leu19Val missense_variant 1/53 ENST00000328300.11 NP_203699.1
COL4A5NM_000495.5 linkuse as main transcriptc.55C>G p.Leu19Val missense_variant 1/51 NP_000486.1
COL4A5XM_047441811.1 linkuse as main transcriptc.55C>G p.Leu19Val missense_variant 1/42 XP_047297767.1
COL4A5XM_047441810.1 linkuse as main transcriptc.-322C>G 5_prime_UTR_variant 1/54 XP_047297766.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL4A5ENST00000328300.11 linkuse as main transcriptc.55C>G p.Leu19Val missense_variant 1/531 NM_033380.3 ENSP00000331902 P29400-2

Frequencies

GnomAD3 genomes
Cov.:
21
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
21

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 submitterclinical testingAmbry GeneticsOct 13, 2023The c.55C>G (p.L19V) alteration is located in exon 1 (coding exon 1) of the COL4A5 gene. This alteration results from a C to G substitution at nucleotide position 55, causing the leucine (L) at amino acid position 19 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
18
DANN
Benign
0.97
DEOGEN2
Benign
0.12
.;T
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.65
T;T
M_CAP
Uncertain
0.19
D
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-0.49
T
MutationAssessor
Benign
0.0
N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.71
N;N
REVEL
Benign
0.25
Sift
Benign
1.0
T;T
Sift4G
Benign
0.19
T;T
Polyphen
0.0010
.;B
Vest4
0.21
MutPred
0.48
Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP
0.51
MPC
0.30
ClinPred
0.20
T
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-107683410; API