Menu
GeneBe

16-4665130-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_015246.4(MGRN1):c.657G>C(p.Val219=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000355 in 1,614,208 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

MGRN1
NM_015246.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0530
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-4665130-G-C is Benign according to our data. Variant chr16-4665130-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2646154.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.053 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MGRN1NM_015246.4 linkuse as main transcriptc.657G>C p.Val219= synonymous_variant 7/17 ENST00000262370.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MGRN1ENST00000262370.12 linkuse as main transcriptc.657G>C p.Val219= synonymous_variant 7/171 NM_015246.4 A1O60291-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000250
AC:
38
AN:
152204
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000412
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000236
AC:
59
AN:
249514
Hom.:
0
AF XY:
0.000170
AC XY:
23
AN XY:
135372
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.000319
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000389
Gnomad OTH exome
AF:
0.000330
GnomAD4 exome
AF:
0.000366
AC:
535
AN:
1461886
Hom.:
0
Cov.:
32
AF XY:
0.000333
AC XY:
242
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000335
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000435
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000249
AC:
38
AN:
152322
Hom.:
0
Cov.:
31
AF XY:
0.000242
AC XY:
18
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000412
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000380
Hom.:
0
Bravo
AF:
0.000257
EpiCase
AF:
0.000491
EpiControl
AF:
0.000296

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJun 01, 2022MGRN1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
Cadd
Benign
1.9
Dann
Benign
0.66

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.

Other links and lift over

dbSNP: rs370162653; hg19: chr16-4715131; API