Variant 16-4652766-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015246.4(MGRN1):c.385C>T(p.Arg129Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000877 in 1,612,072 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R129H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00092 ( 3 hom. )

Consequence

MGRN1
NM_015246.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

Variant links:

Genes affected

MGRN1 (HGNC:20254): (mahogunin ring finger 1) Enables ubiquitin-protein transferase activity. Involved in endosome to lysosome transport; negative regulation of signal transduction; and protein monoubiquitination. Located in several cellular components, including early endosome; endoplasmic reticulum; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MGRN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21506491).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGRN1	NM_015246.4 linkuse as main transcript	c.385C>T	p.Arg129Cys	missense_variant	4/17	ENST00000262370.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGRN1	ENST00000262370.12 linkuse as main transcript	c.385C>T	p.Arg129Cys	missense_variant	4/17	1	NM_015246.4	A1	O60291-2

Frequencies

GnomAD3 genomes

AF:

0.000513

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000911

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000543

AC:

132

AN:

243158

Hom.:

AF XY:

0.000551

AC XY:

AN XY:

132428

show subpopulations

Gnomad AFR exome

AF:

0.000134

Gnomad AMR exome

AF:

0.000118

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000564

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.000915

AC:

1336

AN:

1459776

Hom.:

Cov.:

AF XY:

0.000930

AC XY:

675

AN XY:

726028

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000221

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.00115

Gnomad4 OTH exome

AF:

0.000548

GnomAD4 genome

AF:

0.000512

AC:

AN:

152296

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000911

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.00106

Hom.:

Bravo

AF:

0.000521

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000733

AC:

ESP6500EA

AF:

0.000836

AC:

ExAC

AF:

0.000546

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.385C>T (p.R129C) alteration is located in exon 4 (coding exon 4) of the MGRN1 gene. This alteration results from a C to T substitution at nucleotide position 385, causing the arginine (R) at amino acid position 129 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Uncertain

0.11

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.40

T;.;.;.;D;.;.;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.99

D;D;D;D;D;D;.;D

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.22

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.66

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.85

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D;D;D

Polyphen

1.0

.;D;D;.;D;D;D;.

Vest4

0.92, 0.90, 0.93, 0.90

MVP

0.32

MPC

0.30

ClinPred

0.12

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.52

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