rs953773169

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM1PP3

The NM_020533.3(MCOLN1):c.29C>T(p.Ser10Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 1,368,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

MCOLN1
NM_020533.3 missense, splice_region

Scores

Splicing: ADA: 0.9912

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.12

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: 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

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 3 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity MCLN1_HUMAN

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

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.29C>T	p.Ser10Leu	missense splice_region	Exon 1 of 14	NP_065394.1	Q9GZU1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MCOLN1	ENST00000264079.11	TSL:1 MANE Select	c.29C>T	p.Ser10Leu	missense splice_region	Exon 1 of 14	ENSP00000264079.5	Q9GZU1
MCOLN1	ENST00000596390.1	TSL:1	n.145C>T		splice_region non_coding_transcript_exon	Exon 1 of 2
MCOLN1	ENST00000852002.1		c.29C>T	p.Ser10Leu	missense splice_region	Exon 1 of 14	ENSP00000522061.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000189

AC:

AN:

1216242

Hom.:

Cov.:

AF XY:

0.0000254

AC XY:

AN XY:

590298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24310

American (AMR)

AF:

0.00

AC:

AN:

12226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17852

East Asian (EAS)

AF:

0.00

AC:

AN:

27556

South Asian (SAS)

AF:

0.00

AC:

AN:

53760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28040

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3714

European-Non Finnish (NFE)

AF:

0.0000220

AC:

AN:

998608

Other (OTH)

AF:

0.0000199

AC:

AN:

50176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000340

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.0025

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.019

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.0

PhyloP100

3.1

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.73

REVEL

Benign

0.25

Sift

Benign

0.13

Sift4G

Uncertain

0.047

Polyphen

0.041

Vest4

0.30

MutPred

0.15

Loss of phosphorylation at S10 (P = 0.0143)

MVP

0.83

MPC

0.38

ClinPred

0.59

GERP RS

4.8

PromoterAI

-0.046

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.26

gMVP

0.43

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.78

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over