Variant 16-4664733-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015246.4(MGRN1):c.586G>A(p.Val196Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,614,106 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 1 hom. )

Consequence

MGRN1
NM_015246.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1919955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGRN1	NM_015246.4 linkuse as main transcript	c.586G>A	p.Val196Met	missense_variant	6/17	ENST00000262370.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGRN1	ENST00000262370.12 linkuse as main transcript	c.586G>A	p.Val196Met	missense_variant	6/17	1	NM_015246.4	A1	O60291-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000441

AC:

AN:

249592

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135416

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000530

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Mar 11, 2024

The c.586G>A (p.V196M) alteration is located in exon 6 (coding exon 6) of the MGRN1 gene. This alteration results from a G to A substitution at nucleotide position 586, causing the valine (V) at amino acid position 196 to be replaced by a methionine (M). 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

0.080

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.85

T;T;D;T;T;.

M_CAP

Benign

0.018

MetaRNN

Benign

0.19

T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.5

L;L;.;L;L;L

MutationTaster

Benign

0.95

D;D;D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.0

N;N;.;N;.;.

REVEL

Benign

0.16

Sift

Benign

0.075

T;T;.;T;.;.

Sift4G

Uncertain

0.022

D;D;D;D;D;D

Polyphen

0.098

B;B;.;B;B;B

Vest4

0.43

MVP

0.23

MPC

0.043

ClinPred

0.11

GERP RS

-0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.065

gMVP

0.49

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