chr19-7522782-GT-TC

Position:

• chr19-7522782-GT-TC

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_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
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.94

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]

LOC105372261 (HGNC:):

ACMG classification

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
MCOLN1	NM_020533.3	c.31+1_31+2delGTinsTC		splice_donor_variant, intron_variant		ENST00000264079.11	NP_065394.1
LOC105372261	XR_936293.3	n.936+59_936+60delACinsGA		intron_variant
LOC105372261	XR_936294.3	n.936+59_936+60delACinsGA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCOLN1	ENST00000264079.11	c.31+1_31+2delGTinsTC		splice_donor_variant, intron_variant		1	NM_020533.3	ENSP00000264079.5
MCOLN1	ENST00000596390.1	n.147+1_147+2delGTinsTC		splice_donor_variant, intron_variant		1
MCOLN1	ENST00000601003.1	c.31+1_31+2delGTinsTC		splice_donor_variant, intron_variant		3		ENSP00000469074.1
MCOLN1	ENST00000394321.9	n.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

Submissions by phenotype

Mucolipidosis type IV;C2749050:Lisch epithelial corneal dystrophy Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

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;