chr19-7522757-G-GC
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_020533.3(MCOLN1):c.11dup(p.Ala5GlyfsTer83) 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 (★). Synonymous variant affecting the same amino acid position (i.e. A3A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
MCOLN1
NM_020533.3 frameshift
NM_020533.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.250
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 57 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-7522757-G-GC is Pathogenic according to our data. Variant chr19-7522757-G-GC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1726094.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCOLN1 | NM_020533.3 | c.11dup | p.Ala5GlyfsTer83 | frameshift_variant | 1/14 | ENST00000264079.11 | |
LOC105372261 | XR_936294.3 | n.936+84_936+85insG | intron_variant, non_coding_transcript_variant | ||||
LOC105372261 | XR_936293.3 | n.936+84_936+85insG | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCOLN1 | ENST00000264079.11 | c.11dup | p.Ala5GlyfsTer83 | frameshift_variant | 1/14 | 1 | NM_020533.3 | P1 | |
MCOLN1 | ENST00000596390.1 | n.127dup | non_coding_transcript_exon_variant | 1/2 | 1 | ||||
MCOLN1 | ENST00000601003.1 | c.11dup | p.Ala5GlyfsTer83 | frameshift_variant | 1/5 | 3 | |||
MCOLN1 | ENST00000394321.9 | n.91dup | non_coding_transcript_exon_variant | 1/13 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Mucolipidosis type IV Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | May 18, 2022 | NM_020533.2(MCOLN1):c.11dupC(A5Gfs*83) is expected to be pathogenic in the context of mucolipidosis IV. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in MCOLN1, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening. - |
Computational scores
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Calibrated prediction
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Prediction
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
Publications
No publications associated with this variant yet.