chr19-7522782-GT-TC

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_020533.3(MCOLN1):​c.31+1_31+2delGTinsTC variant causes a splice donor, intron change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MCOLN1
NM_020533.3 splice_donor, intron

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 3.94
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-7522782-GT-TC is Pathogenic according to our data. Variant chr19-7522782-GT-TC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3584202.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MCOLN1NM_020533.3 linkc.31+1_31+2delGTinsTC splice_donor_variant, intron_variant ENST00000264079.11 NP_065394.1 Q9GZU1
LOC105372261XR_936293.3 linkn.936+59_936+60delACinsGA intron_variant
LOC105372261XR_936294.3 linkn.936+59_936+60delACinsGA intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MCOLN1ENST00000264079.11 linkc.31+1_31+2delGTinsTC splice_donor_variant, intron_variant 1 NM_020533.3 ENSP00000264079.5 Q9GZU1
MCOLN1ENST00000596390.1 linkn.147+1_147+2delGTinsTC splice_donor_variant, intron_variant 1
MCOLN1ENST00000601003.1 linkc.31+1_31+2delGTinsTC splice_donor_variant, intron_variant 3 ENSP00000469074.1 M0QXD0
MCOLN1ENST00000394321.9 linkn.111+1_111+2delGTinsTC splice_donor_variant, intron_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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;C2749050:Lisch epithelial corneal dystrophy Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsMay 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-7587668; API