Variant 1-204549118-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002393.5(MDM4):c.909G>A(p.Glu303=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,592,810 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 14 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 100 hom. )

Consequence

MDM4
NM_002393.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.428

Variant links:

Genes affected

MDM4 (HGNC:6974): (MDM4 regulator of p53) This gene encodes a nuclear protein that contains a p53 binding domain at the N-terminus and a RING finger domain at the C-terminus, and shows structural similarity to p53-binding protein MDM2. Both proteins bind the p53 tumor suppressor protein and inhibit its activity, and have been shown to be overexpressed in a variety of human cancers. However, unlike MDM2 which degrades p53, this protein inhibits p53 by binding its transcriptional activation domain. This protein also interacts with MDM2 protein via the RING finger domain, and inhibits the latter's degradation. So this protein can reverse MDM2-targeted degradation of p53, while maintaining suppression of p53 transactivation and apoptotic functions. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Feb 2011]

MDM4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 1-204549118-G-A is Benign according to our data. Variant chr1-204549118-G-A is described in ClinVar as [Benign]. Clinvar id is 770500.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.428 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDM4	NM_002393.5 linkuse as main transcript	c.909G>A	p.Glu303=	synonymous_variant	11/11	ENST00000367182.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDM4	ENST00000367182.8 linkuse as main transcript	c.909G>A	p.Glu303=	synonymous_variant	11/11	1	NM_002393.5	P1	O15151-1

Frequencies

GnomAD3 genomes

AF:

0.00359

AC:

546

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0312

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:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00984

AC:

2365

AN:

240306

Hom.:

AF XY:

0.00712

AC XY:

924

AN XY:

129798

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.0707

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000911

Gnomad OTH exome

AF:

0.00749

GnomAD4 exome

AF:

0.00205

AC:

2959

AN:

1440516

Hom.:

100

Cov.:

AF XY:

0.00169

AC XY:

1211

AN XY:

716478

show subpopulations

Gnomad4 AFR exome

AF:

0.000886

Gnomad4 AMR exome

AF:

0.0668

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000273

Gnomad4 OTH exome

AF:

0.00153

GnomAD4 genome

AF:

0.00359

AC:

547

AN:

152294

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

310

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.0313

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00122

Hom.:

Bravo

AF:

0.00682

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

Cadd

Benign

5.5

Dann

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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