Genetic Variant MREG:p.Arg188Gln (chr2-215944945-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_018000.3(MREG):c.563G>A(p.Arg188Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000678 in 1,607,552 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 1 hom. )

Consequence

MREG
NM_018000.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.66

Publications

7 publications found

Variant links:

Genes affected

MREG (HGNC:25478): (melanoregulin) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in melanocyte differentiation; melanosome transport; and phagosome maturation. Predicted to act upstream of or within developmental pigmentation. Predicted to be located in late endosome membrane and melanosome membrane. Predicted to be intrinsic component of organelle membrane. Predicted to be part of protein-containing complex. Predicted to be active in melanosome. [provided by Alliance of Genome Resources, Apr 2022]

MREG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017011553).

BP6

Variant 2-215944945-C-T is Benign according to our data. Variant chr2-215944945-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2533554.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018000.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MREG	NM_018000.3	MANE Select	c.563G>A	p.Arg188Gln	missense	Exon 5 of 5	NP_060470.2	Q8N565-1
MREG	NM_001372188.1		c.713G>A	p.Arg238Gln	missense	Exon 6 of 6	NP_001359117.1
MREG	NM_001372189.1		c.401G>A	p.Arg134Gln	missense	Exon 5 of 5	NP_001359118.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MREG	ENST00000263268.11	TSL:2 MANE Select	c.563G>A	p.Arg188Gln	missense	Exon 5 of 5	ENSP00000263268.6	Q8N565-1
MREG	ENST00000439791.5	TSL:4	c.*14G>A		downstream_gene	N/A	ENSP00000411076.1	C9JAG4
MREG	ENST00000424992.5	TSL:5	c.*43G>A		downstream_gene	N/A	ENSP00000413302.1	C9JYV9

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000924

AC:

AN:

248918

AF XY:

0.000118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000621

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000680

AC:

AN:

1455398

Hom.:

Cov.:

AF XY:

0.0000885

AC XY:

AN XY:

723188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33422

American (AMR)

AF:

0.00

AC:

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39582

South Asian (SAS)

AF:

0.000571

AC:

AN:

85754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53266

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.0000425

AC:

AN:

1106848

Other (OTH)

AF:

0.0000333

AC:

AN:

60090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000657

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0000964

AC:

AN:

41510

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000415

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.0000900

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000579

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.9

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.20

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.72

M_CAP

Benign

0.0098

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.14

PhyloP100

-2.7

PrimateAI

Benign

0.19

PROVEAN

Benign

-1.6

REVEL

Benign

0.018

Sift

Benign

0.39

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.11

MutPred

0.24

Gain of ubiquitination at K193 (P = 0.1028)

MVP

0.11

MPC

0.090

ClinPred

0.61

GERP RS

-3.8

Varity_R

0.025

gMVP

0.098

Mutation Taster

=97/3

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

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