Variant rs2306392 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001354969.2(MDM1):c.1685C>T(p.Pro562Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,611,628 control chromosomes in the GnomAD database, including 72,222 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4812 hom., cov: 32)

Exomes 𝑓: 0.30 ( 67410 hom. )

Consequence

MDM1
NM_001354969.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.10

Variant links:

Genes affected

MDM1 (HGNC:29917): (Mdm1 nuclear protein) This gene encodes a microtubule-binding nuclear protein that localizes to the centrioles of dividing cells and differentiating multiciliated cells and negatively regulates centriole duplication. The encoded protein is closely associated with the centriole barrel, and resides in the centriole lumen. Naturally-occurring mutations in the orthologous mouse gene are associated with age-related retinal degeneration. [provided by RefSeq, Feb 2019]

MDM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005428165).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDM1	NM_001354969.2 linkuse as main transcript	c.1685C>T	p.Pro562Leu	missense_variant	12/15	ENST00000682720.1	NP_001341898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDM1	ENST00000682720.1 linkuse as main transcript	c.1685C>T	p.Pro562Leu	missense_variant	12/15		NM_001354969.2	ENSP00000507100	P1

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

35956

AN:

151990

Hom.:

4816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.282

GnomAD3 exomes

AF:

0.272

AC:

68261

AN:

251250

Hom.:

10171

AF XY:

0.285

AC XY:

38670

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.197

Gnomad ASJ exome

AF:

0.388

Gnomad EAS exome

AF:

0.158

Gnomad SAS exome

AF:

0.367

Gnomad FIN exome

AF:

0.193

Gnomad NFE exome

AF:

0.312

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.298

AC:

435356

AN:

1459518

Hom.:

67410

Cov.:

AF XY:

0.302

AC XY:

219250

AN XY:

726150

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.380

Gnomad4 EAS exome

AF:

0.187

Gnomad4 SAS exome

AF:

0.364

Gnomad4 FIN exome

AF:

0.201

Gnomad4 NFE exome

AF:

0.308

Gnomad4 OTH exome

AF:

0.305

GnomAD4 genome

AF:

0.236

AC:

35961

AN:

152110

Hom.:

4812

Cov.:

AF XY:

0.232

AC XY:

17267

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.394

Gnomad4 EAS

AF:

0.173

Gnomad4 SAS

AF:

0.346

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.302

Gnomad4 OTH

AF:

0.284

Alfa

AF:

0.302

Hom.:

18485

Bravo

AF:

0.234

TwinsUK

AF:

0.311

AC:

1155

ALSPAC

AF:

0.306

AC:

1181

ESP6500AA

AF:

0.126

AC:

557

ESP6500EA

AF:

0.313

AC:

2693

ExAC

AF:

0.275

AC:

33352

Asia WGS

AF:

0.273

AC:

955

AN:

3478

EpiCase

AF:

0.327

EpiControl

AF:

0.326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.23

DEOGEN2

Benign

0.36

T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.99

L;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.25

PROVEAN

Uncertain

-2.5

D;N

REVEL

Benign

0.12

Sift

Benign

0.47

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.0030

B;.

Vest4

0.032

MPC

0.048

ClinPred

0.016

GERP RS

2.2

Varity_R

0.028

gMVP

0.098

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over