rs61736600

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020533.3(MCOLN1):c.966A>C(p.Arg322Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0709 in 1,613,996 control chromosomes in the GnomAD database, including 4,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R322R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.059 ( 320 hom., cov: 33)

Exomes 𝑓: 0.072 ( 4280 hom. )

Consequence

MCOLN1
NM_020533.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -3.37

Publications

11 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 19-7528685-A-C is Benign according to our data. Variant chr19-7528685-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCOLN1	NM_020533.3 link	c.966A>C	p.Arg322Arg	synonymous_variant	Exon 8 of 14	ENST00000264079.11	NP_065394.1	Q9GZU1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MCOLN1	ENST00000264079.11 link	c.966A>C	p.Arg322Arg	synonymous_variant	Exon 8 of 14	1	NM_020533.3	ENSP00000264079.5	Q9GZU1
MCOLN1	ENST00000394321.9 link	n.1281A>C		non_coding_transcript_exon_variant	Exon 7 of 13	2
MCOLN1	ENST00000595860.5 link	n.32A>C		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.0591

AC:

8988

AN:

152052

Hom.:

318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0363

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0654

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0201

Gnomad FIN

AF:

0.0345

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0796

Gnomad OTH

AF:

0.0698

GnomAD2 exomes

AF:

0.0561

AC:

14099

AN:

251278

AF XY:

0.0570

show subpopulations

Gnomad AFR exome

AF:

0.0346

Gnomad AMR exome

AF:

0.0461

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.000489

Gnomad FIN exome

AF:

0.0356

Gnomad NFE exome

AF:

0.0797

Gnomad OTH exome

AF:

0.0699

GnomAD4 exome

AF:

0.0722

AC:

105513

AN:

1461826

Hom.:

4280

Cov.:

AF XY:

0.0710

AC XY:

51627

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.0369

AC:

1234

AN:

33480

American (AMR)

AF:

0.0469

AC:

2096

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

2891

AN:

26136

East Asian (EAS)

AF:

0.000302

AC:

AN:

39700

South Asian (SAS)

AF:

0.0213

AC:

1835

AN:

86254

European-Finnish (FIN)

AF:

0.0395

AC:

2111

AN:

53400

Middle Eastern (MID)

AF:

0.0669

AC:

386

AN:

5768

European-Non Finnish (NFE)

AF:

0.0816

AC:

90787

AN:

1111974

Other (OTH)

AF:

0.0689

AC:

4161

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

6190

12380

18570

24760

30950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3272

6544

9816

13088

16360

<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:

0.0591

AC:

8990

AN:

152170

Hom.:

320

Cov.:

AF XY:

0.0563

AC XY:

4187

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0363

AC:

1505

AN:

41498

American (AMR)

AF:

0.0652

AC:

998

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

383

AN:

3472

East Asian (EAS)

AF:

0.000388

AC:

AN:

5158

South Asian (SAS)

AF:

0.0210

AC:

101

AN:

4816

European-Finnish (FIN)

AF:

0.0345

AC:

366

AN:

10606

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0796

AC:

5413

AN:

68002

Other (OTH)

AF:

0.0686

AC:

145

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

477

954

1432

1909

2386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0586

Hom.:

148

Bravo

AF:

0.0611

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0824

EpiControl

AF:

0.0885

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mucolipidosis type IV

Benign:5

Aug 13, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 25, 2017

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 26, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.091

(source)

DANN

Benign

0.48

PhyloP100

-3.4

PromoterAI

0.096

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over