rs612862

Positions:

chr19-7528703-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020533.3(MCOLN1):c.984C>T(p.Asn328=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,613,998 control chromosomes in the GnomAD database, including 79,402 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6634 hom., cov: 34)

Exomes 𝑓: 0.31 ( 72768 hom. )

Consequence

MCOLN1
NM_020533.3 splice_region, synonymous

Scores

Splicing: ADA: 0.00006245

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.10

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 19-7528703-C-T is Benign according to our data. Variant chr19-7528703-C-T is described in ClinVar as [Benign]. Clinvar id is 261324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-7528703-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCOLN1	NM_020533.3 linkuse as main transcript	c.984C>T	p.Asn328=	splice_region_variant, synonymous_variant	8/14	ENST00000264079.11	NP_065394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MCOLN1	ENST00000264079.11 linkuse as main transcript	c.984C>T	p.Asn328=	splice_region_variant, synonymous_variant	8/14	1	NM_020533.3	ENSP00000264079	P1
MCOLN1	ENST00000394321.9 linkuse as main transcript	n.1299C>T		splice_region_variant, non_coding_transcript_exon_variant	7/13	2
MCOLN1	ENST00000595860.5 linkuse as main transcript	n.50C>T		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.287

AC:

43718

AN:

152110

Hom.:

6643

Cov.:

show subpopulations

Gnomad AFR

AF:

0.240

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.324

GnomAD3 exomes

AF:

0.284

AC:

71289

AN:

251070

Hom.:

11073

AF XY:

0.292

AC XY:

39573

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.172

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.158

Gnomad SAS exome

AF:

0.276

Gnomad FIN exome

AF:

0.275

Gnomad NFE exome

AF:

0.336

Gnomad OTH exome

AF:

0.329

GnomAD4 exome

AF:

0.311

AC:

454662

AN:

1461768

Hom.:

72768

Cov.:

AF XY:

0.312

AC XY:

226952

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.232

Gnomad4 AMR exome

AF:

0.181

Gnomad4 ASJ exome

AF:

0.403

Gnomad4 EAS exome

AF:

0.138

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.279

Gnomad4 NFE exome

AF:

0.326

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.287

AC:

43713

AN:

152230

Hom.:

6634

Cov.:

AF XY:

0.285

AC XY:

21207

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.240

Gnomad4 AMR

AF:

0.253

Gnomad4 ASJ

AF:

0.414

Gnomad4 EAS

AF:

0.150

Gnomad4 SAS

AF:

0.276

Gnomad4 FIN

AF:

0.274

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.321

Alfa

AF:

0.325

Hom.:

17592

Bravo

AF:

0.282

Asia WGS

AF:

0.236

AC:

822

AN:

3478

EpiCase

AF:

0.347

EpiControl

AF:

0.351

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mucolipidosis type IV

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Apr 25, 2017	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 23, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.35

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000062

dbscSNV1_RF

Benign

0.012

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over