Variant chr16-4652694-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015246.4(MGRN1):c.313G>A(p.Asp105Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000417 in 1,612,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 0 hom. )

Consequence

MGRN1
NM_015246.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.94

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06582394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGRN1	NM_015246.4 linkuse as main transcript	c.313G>A	p.Asp105Asn	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.313G>A	p.Asp105Asn	missense_variant	4/17	1	NM_015246.4	A1	O60291-2

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000359

AC:

AN:

245326

Hom.:

AF XY:

0.000427

AC XY:

AN XY:

133612

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000561

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.000143

Gnomad NFE exome

AF:

0.000713

Gnomad OTH exome

AF:

0.000504

GnomAD4 exome

AF:

0.000398

AC:

582

AN:

1460486

Hom.:

Cov.:

AF XY:

0.000413

AC XY:

300

AN XY:

726558

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000898

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000451

Gnomad4 NFE exome

AF:

0.000479

Gnomad4 OTH exome

AF:

0.000332

GnomAD4 genome

AF:

0.000598

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000565

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000652

Hom.:

Bravo

AF:

0.000359

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000715

AC:

ExAC

AF:

0.000405

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000654

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

Aug 12, 2021

The c.313G>A (p.D105N) alteration is located in exon 4 (coding exon 4) of the MGRN1 gene. This alteration results from a G to A substitution at nucleotide position 313, causing the aspartic acid (D) at amino acid position 105 to be replaced by an asparagine (N). 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

0.071

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.075

T;.;.;.;T;.;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.10

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

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

M_CAP

Benign

0.028

MetaRNN

Benign

0.066

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

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.44

Sift4G

Benign

0.088

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

Polyphen

0.067, 0.048, 0.075, 0.027

.;B;B;.;B;B;B;.

Vest4

0.49, 0.44, 0.45, 0.45, 0.44

MVP

0.25

MPC

0.053

ClinPred

0.046

GERP RS

4.5

Varity_R

0.092

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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