19-7522783-T-TGAG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_020533.3(MCOLN1):c.31+4_31+6dup variant causes a splice region, intron 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 benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MCOLN1 NM_020533.3 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.54

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-7522783-T-TGAG is Benign according to our data. Variant chr19-7522783-T-TGAG is described in ClinVar as [Likely_benign]. Clinvar id is 1089824.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.31+4_31+6dup		splice_region_variant, intron_variant		ENST00000264079.11
LOC105372261	XR_936294.3	n.936+58_936+59insCTC		intron_variant, non_coding_transcript_variant
LOC105372261	XR_936293.3	n.936+58_936+59insCTC		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCOLN1	ENST00000264079.11	c.31+4_31+6dup		splice_region_variant, intron_variant		1	NM_020533.3	P1
MCOLN1	ENST00000596390.1	n.147+4_147+6dup		splice_region_variant, intron_variant, non_coding_transcript_variant		1
MCOLN1	ENST00000601003.1	c.31+4_31+6dup		splice_region_variant, intron_variant		3
MCOLN1	ENST00000394321.9	n.111+4_111+6dup		splice_region_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mucolipidosis type IV Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 07, 2020

- -

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: chr19-7587669;