chrX-50042394-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001127898.4(CLCN5):c.95A>G(p.Asp32Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000259 in 1,161,946 control chromosomes in the GnomAD database, including 1 homozygotes. There are 99 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00034 ( 1 hom., 9 hem., cov: 22)
Exomes 𝑓: 0.00025 ( 0 hom. 90 hem. )
Consequence
CLCN5
NM_001127898.4 missense
NM_001127898.4 missense
Scores
1
5
8
Clinical Significance
Conservation
PhyloP100: 7.03
Genes affected
CLCN5 (HGNC:2023): (chloride voltage-gated channel 5) This gene encodes a member of the ClC family of chloride ion channels and ion transporters. The encoded protein is primarily localized to endosomal membranes and may function to facilitate albumin uptake by the renal proximal tubule. Mutations in this gene have been found in Dent disease and renal tubular disorders complicated by nephrolithiasis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008176386).
BP6
?
Variant X-50042394-A-G is Benign according to our data. Variant chrX-50042394-A-G is described in ClinVar as [Benign]. Clinvar id is 3048658.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00034 (38/111825) while in subpopulation NFE AF= 0.00015 (8/53163). AF 95% confidence interval is 0.0000745. There are 1 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd at 9 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLCN5 | NM_001127898.4 | c.95A>G | p.Asp32Gly | missense_variant | 4/15 | ENST00000376091.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCN5 | ENST00000376091.8 | c.95A>G | p.Asp32Gly | missense_variant | 4/15 | 2 | NM_001127898.4 | P3 | |
CLCN5 | ENST00000376088.7 | c.95A>G | p.Asp32Gly | missense_variant | 4/15 | 2 | P3 | ||
CLCN5 | ENST00000482218.2 | c.95A>G | p.Asp32Gly | missense_variant | 3/3 | 3 | |||
CLCN5 | ENST00000643129.1 | c.59A>G | p.Asp20Gly | missense_variant, NMD_transcript_variant | 1/14 |
Frequencies
GnomAD3 genomes ? AF: 0.000340 AC: 38AN: 111825Hom.: 1 Cov.: 22 AF XY: 0.000265 AC XY: 9AN XY: 34007
GnomAD3 genomes
?
AF:
AC:
38
AN:
111825
Hom.:
Cov.:
22
AF XY:
AC XY:
9
AN XY:
34007
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000563 AC: 68AN: 120844Hom.: 0 AF XY: 0.000635 AC XY: 22AN XY: 34666
GnomAD3 exomes
AF:
AC:
68
AN:
120844
Hom.:
AF XY:
AC XY:
22
AN XY:
34666
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000250 AC: 263AN: 1050121Hom.: 0 Cov.: 26 AF XY: 0.000270 AC XY: 90AN XY: 333839
GnomAD4 exome
AF:
AC:
263
AN:
1050121
Hom.:
Cov.:
26
AF XY:
AC XY:
90
AN XY:
333839
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000340 AC: 38AN: 111825Hom.: 1 Cov.: 22 AF XY: 0.000265 AC XY: 9AN XY: 34007
GnomAD4 genome
?
AF:
AC:
38
AN:
111825
Hom.:
Cov.:
22
AF XY:
AC XY:
9
AN XY:
34007
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
3
ALSPAC
AF:
AC:
0
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
4
ExAC
?
AF:
AC:
46
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CLCN5-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 11, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.
REVEL
Uncertain
Sift
Uncertain
D;D;.
Sift4G
Benign
T;T;T
Polyphen
B;B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at