rs121434432
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001287.6(CLCN7):c.1663C>T(p.Gln555*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,433,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
CLCN7
NM_001287.6 stop_gained
NM_001287.6 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 9.55
Genes affected
CLCN7 (HGNC:2025): (chloride voltage-gated channel 7) The product of this gene belongs to the CLC chloride channel family of proteins. Chloride channels play important roles in the plasma membrane and in intracellular organelles. This gene encodes chloride channel 7. Defects in this gene are the cause of osteopetrosis autosomal recessive type 4 (OPTB4), also called infantile malignant osteopetrosis type 2 as well as the cause of autosomal dominant osteopetrosis type 2 (OPTA2), also called autosomal dominant Albers-Schonberg disease or marble disease autosoml dominant. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. OPTA2 is the most common form of osteopetrosis, occurring in adolescence or adulthood. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-1449282-G-A is Pathogenic according to our data. Variant chr16-1449282-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 6860.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CLCN7 | NM_001287.6 | c.1663C>T | p.Gln555* | stop_gained | 18/25 | ENST00000382745.9 | NP_001278.1 | |
CLCN7 | NM_001114331.3 | c.1591C>T | p.Gln531* | stop_gained | 17/24 | NP_001107803.1 | ||
CLCN7 | XM_011522354.2 | c.1489C>T | p.Gln497* | stop_gained | 18/25 | XP_011520656.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CLCN7 | ENST00000382745.9 | c.1663C>T | p.Gln555* | stop_gained | 18/25 | 1 | NM_001287.6 | ENSP00000372193.4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.97e-7 AC: 1AN: 1433864Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 710868
GnomAD4 exome
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1
AN:
1433864
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34
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0
AN XY:
710868
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive osteopetrosis 4 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 26, 2001 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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