19-7522663-G-C

Variant names:

• chr19-7522663-G-C
• rs886054691
• NM_020533.3:c.-88G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020533.3(MCOLN1):​c.-88G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000419 in 1,194,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: MCOLN1 NM_020533.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 0 publications found

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: G2P, ClinGen, Genomics England PanelApp, Ambry Genetics, Myriad Women’s Health, Orphanet, Labcorp Genetics (formerly Invitae)
• Lisch epithelial corneal dystrophy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000305089 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020533.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCOLN1	NM_020533.3	MANE Select	c.-88G>C		5_prime_UTR	Exon 1 of 14	NP_065394.1	Q9GZU1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCOLN1	ENST00000264079.11	TSL:1 MANE Select	c.-88G>C		5_prime_UTR	Exon 1 of 14	ENSP00000264079.5	Q9GZU1
	MCOLN1	ENST00000596390.1	TSL:1	n.29G>C		non_coding_transcript_exon	Exon 1 of 2
	MCOLN1	ENST00000852002.1		c.-88G>C		5_prime_UTR	Exon 1 of 14	ENSP00000522061.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000419 AC: 5 AN: 1194510 Hom.: 0 Cov.: 17 AF XY: 0.00000170 AC XY: 1 AN XY: 587568

African (AFR) AF: 0.00 AC: 0 AN: 24106

American (AMR) AF: 0.0000482 AC: 1 AN: 20754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20118

East Asian (EAS) AF: 0.00 AC: 0 AN: 28038

South Asian (SAS) AF: 0.00 AC: 0 AN: 63158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3578

European-Non Finnish (NFE) AF: 0.00000419 AC: 4 AN: 953908

Other (OTH) AF: 0.00 AC: 0 AN: 50150

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.80
PhyloP100		-0.12
PromoterAI		-0.043	Neutral

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

Other links and lift over

dbSNP: rs886054691; hg19: chr19-7587549;