Variant 1-84939570-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_153259.4(MCOLN2):c.1093A>G(p.Met365Val) variant causes a missense change. The variant allele was found at a frequency of 0.00509 in 1,613,904 control chromosomes in the GnomAD database, including 379 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.027 ( 215 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 164 hom. )

Consequence

MCOLN2
NM_153259.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.95

Variant links:

Genes affected

MCOLN2 (HGNC:13357): (mucolipin TRP cation channel 2) Mucolipins constitute a family of cation channel proteins with homology to the transient receptor potential superfamily. In mammals, the mucolipin family includes 3 members, MCOLN1 (MIM 605248), MCOLN2, and MCOLN3 (MIM 607400), that exhibit a common 6-membrane-spanning topology. Homologs of mammalian mucolipins exist in Drosophila and C. elegans. Mutations in the human MCOLN1 gene cause mucolipodosis IV (MIM 262650) (Karacsonyi et al., 2007 [PubMed 17662026]).[supplied by OMIM, Sep 2009]

MCOLN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027332306).

BP6

Variant 1-84939570-T-C is Benign according to our data. Variant chr1-84939570-T-C is described in ClinVar as [Benign]. Clinvar id is 787751.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCOLN2	NM_153259.4 linkuse as main transcript	c.1093A>G	p.Met365Val	missense_variant	9/14	ENST00000370608.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCOLN2	ENST00000370608.8 linkuse as main transcript	c.1093A>G	p.Met365Val	missense_variant	9/14	1	NM_153259.4		Q8IZK6-1
MCOLN2	ENST00000531325.5 linkuse as main transcript	n.1334A>G		non_coding_transcript_exon_variant	9/12	1
MCOLN2	ENST00000284027.5 linkuse as main transcript	c.1009A>G	p.Met337Val	missense_variant	9/14	5		P1	Q8IZK6-2
MCOLN2	ENST00000463065.5 linkuse as main transcript	c.*45-1488A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0271

AC:

4128

AN:

152136

Hom.:

216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0946

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.00682

AC:

1713

AN:

251004

Hom.:

AF XY:

0.00511

AC XY:

693

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.0937

Gnomad AMR exome

AF:

0.00389

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00279

AC:

4079

AN:

1461650

Hom.:

164

Cov.:

AF XY:

0.00243

AC XY:

1770

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.0960

Gnomad4 AMR exome

AF:

0.00497

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000222

Gnomad4 OTH exome

AF:

0.00598

GnomAD4 genome

AF:

0.0271

AC:

4132

AN:

152254

Hom.:

215

Cov.:

AF XY:

0.0257

AC XY:

1910

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0944

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.00622

Hom.:

Bravo

AF:

0.0308

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0978

AC:

431

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00858

AC:

1042

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.24

Cadd

Benign

Dann

Benign

0.87

DEOGEN2

Benign

0.0034

T;.

Eigen

Benign

0.096

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.84

T;D

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-0.37

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.57

N;N

REVEL

Uncertain

0.30

Sift

Benign

0.25

T;T

Sift4G

Benign

0.71

T;T

Polyphen

0.067

B;.

Vest4

0.23

MVP

0.86

MPC

0.084

ClinPred

0.016

GERP RS

5.2

Varity_R

0.18

gMVP

0.82

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

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