NM_020533.3:c.11C>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020533.3(MCOLN1):c.11C>T(p.Pro4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000236 in 1,271,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P4Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

MCOLN1
NM_020533.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0390

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

MCOLN1 links:

ENSG00000305089 (HGNC:):

ENSG00000305089 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 (MetaRNN=0.1726293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCOLN1	NM_020533.3 link	c.11C>T	p.Pro4Leu	missense_variant	Exon 1 of 14	ENST00000264079.11	NP_065394.1	Q9GZU1
LOC105372261	XR_936293.3 link	n.936+81G>A		intron_variant	Intron 2 of 2
LOC105372261	XR_936294.3 link	n.936+81G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCOLN1	ENST00000264079.11 link	c.11C>T	p.Pro4Leu	missense_variant	Exon 1 of 14	1	NM_020533.3	ENSP00000264079.5		Q9GZU1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000236

AC:

AN:

1271358

Hom.:

Cov.:

AF XY:

0.00000483

AC XY:

AN XY:

621094

show subpopulations

African (AFR)

AF:

0.0000386

AC:

AN:

25898

American (AMR)

AF:

0.00

AC:

AN:

21514

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20940

East Asian (EAS)

AF:

0.00

AC:

AN:

28196

South Asian (SAS)

AF:

0.00

AC:

AN:

64010

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3850

European-Non Finnish (NFE)

AF:

0.00000195

AC:

AN:

1023946

Other (OTH)

AF:

0.00

AC:

AN:

52792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Apr 07, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.11C>T (p.P4L) alteration is located in exon 1 (coding exon 1) of the MCOLN1 gene. This alteration results from a C to T substitution at nucleotide position 11, causing the proline (P) at amino acid position 4 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.56

T;T

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.1

L;.

PhyloP100

0.039

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.91

N;.

REVEL

Benign

0.17

Sift

Uncertain

0.022

D;.

Sift4G

Benign

0.065

T;D

Polyphen

0.012

B;.

Vest4

0.10

MutPred

0.20

Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);

MVP

0.73

MPC

0.43

ClinPred

0.21

GERP RS

3.8

PromoterAI

0.040

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.11

gMVP

0.52

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over