19-7522757-GC-G
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_020533.3(MCOLN1):c.11delC(p.Pro4ArgfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MCOLN1
NM_020533.3 frameshift
NM_020533.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.250
Publications
0 publications found
Genes affected
MCOLN1 (HGNC:13356): (mucolipin TRP cation channel 1) This gene encodes a memberof the transient receptor potential (TRP) cation channel gene family. The transmembrane protein localizes to intracellular vesicular membranes including lysosomes, and functions in the late endocytic pathway and in the regulation of lysosomal exocytosis. The channel is permeable to Ca(2+), Fe(2+), Na(+), K(+), and H(+), and is modulated by changes in Ca(2+) concentration. Mutations in this gene result in mucolipidosis type IV. [provided by RefSeq, Oct 2009]
MCOLN1 Gene-Disease associations (from GenCC):
- mucolipidosis type IVInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, ClinGen, G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
- Lisch epithelial corneal dystrophyInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 89 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-7522757-GC-G is Pathogenic according to our data. Variant chr19-7522757-GC-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 4057590.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MCOLN1 | NM_020533.3 | c.11delC | p.Pro4ArgfsTer13 | frameshift_variant | Exon 1 of 14 | ENST00000264079.11 | NP_065394.1 | |
LOC105372261 | XR_936293.3 | n.936+84delG | intron_variant | Intron 2 of 2 | ||||
LOC105372261 | XR_936294.3 | n.936+84delG | intron_variant | Intron 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1277096Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 624460
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1277096
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
624460
African (AFR)
AF:
AC:
0
AN:
25978
American (AMR)
AF:
AC:
0
AN:
22124
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
21412
East Asian (EAS)
AF:
AC:
0
AN:
28234
South Asian (SAS)
AF:
AC:
0
AN:
65220
European-Finnish (FIN)
AF:
AC:
0
AN:
30452
Middle Eastern (MID)
AF:
AC:
0
AN:
3842
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1026784
Other (OTH)
AF:
AC:
0
AN:
53050
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Mucolipidosis type IV Pathogenic:1
Jan 13, 2025
Natera, Inc.
Significance:Likely pathogenic
Review Status:no assertion criteria provided
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
Publications
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