19-7522757-GC-G

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

Scores

Not classified

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.250

Publications

0 publications found
Variant links:
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 IV
    Inheritance: 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 dystrophy
    Inheritance: 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
MCOLN1NM_020533.3 linkc.11delC p.Pro4ArgfsTer13 frameshift_variant Exon 1 of 14 ENST00000264079.11 NP_065394.1 Q9GZU1
LOC105372261XR_936293.3 linkn.936+84delG intron_variant Intron 2 of 2
LOC105372261XR_936294.3 linkn.936+84delG intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MCOLN1ENST00000264079.11 linkc.11delC p.Pro4ArgfsTer13 frameshift_variant Exon 1 of 14 1 NM_020533.3 ENSP00000264079.5 Q9GZU1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1277096
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
624460
African (AFR)
AF:
0.00
AC:
0
AN:
25978
American (AMR)
AF:
0.00
AC:
0
AN:
22124
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
21412
East Asian (EAS)
AF:
0.00
AC:
0
AN:
28234
South Asian (SAS)
AF:
0.00
AC:
0
AN:
65220
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
30452
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3842
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1026784
Other (OTH)
AF:
0.00
AC:
0
AN:
53050
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

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.25

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

Other links and lift over

hg19: chr19-7587643; API