Variant rs962976 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001354969.2(MDM1):c.308C>T(p.Thr103Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,613,840 control chromosomes in the GnomAD database, including 410,347 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 40523 hom., cov: 31)

Exomes 𝑓: 0.71 ( 369824 hom. )

Consequence

MDM1
NM_001354969.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0860

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3557108E-6).

BP6

Variant 12-68326847-G-A is Benign according to our data. Variant chr12-68326847-G-A is described in ClinVar as [Benign]. Clinvar id is 1247123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 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.308C>T	p.Thr103Ile	missense_variant	3/15	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.308C>T	p.Thr103Ile	missense_variant	3/15		NM_001354969.2	ENSP00000507100	P1

Frequencies

GnomAD3 genomes

AF:

0.727

AC:

110385

AN:

151928

Hom.:

40486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.791

Gnomad AMI

AF:

0.828

Gnomad AMR

AF:

0.722

Gnomad ASJ

AF:

0.753

Gnomad EAS

AF:

0.450

Gnomad SAS

AF:

0.682

Gnomad FIN

AF:

0.738

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.708

Gnomad OTH

AF:

0.742

GnomAD3 exomes

AF:

0.693

AC:

174311

AN:

251384

Hom.:

61591

AF XY:

0.696

AC XY:

94610

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.797

Gnomad AMR exome

AF:

0.676

Gnomad ASJ exome

AF:

0.755

Gnomad EAS exome

AF:

0.413

Gnomad SAS exome

AF:

0.698

Gnomad FIN exome

AF:

0.731

Gnomad NFE exome

AF:

0.714

Gnomad OTH exome

AF:

0.716

GnomAD4 exome

AF:

0.710

AC:

1037675

AN:

1461794

Hom.:

369824

Cov.:

AF XY:

0.711

AC XY:

516725

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.795

Gnomad4 AMR exome

AF:

0.686

Gnomad4 ASJ exome

AF:

0.756

Gnomad4 EAS exome

AF:

0.516

Gnomad4 SAS exome

AF:

0.701

Gnomad4 FIN exome

AF:

0.724

Gnomad4 NFE exome

AF:

0.714

Gnomad4 OTH exome

AF:

0.705

GnomAD4 genome

AF:

0.727

AC:

110477

AN:

152046

Hom.:

40523

Cov.:

AF XY:

0.726

AC XY:

53923

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.791

Gnomad4 AMR

AF:

0.722

Gnomad4 ASJ

AF:

0.753

Gnomad4 EAS

AF:

0.449

Gnomad4 SAS

AF:

0.683

Gnomad4 FIN

AF:

0.738

Gnomad4 NFE

AF:

0.708

Gnomad4 OTH

AF:

0.739

Alfa

AF:

0.712

Hom.:

99747

Bravo

AF:

0.728

TwinsUK

AF:

0.703

AC:

2606

ALSPAC

AF:

0.708

AC:

2728

ESP6500AA

AF:

0.785

AC:

3459

ESP6500EA

AF:

0.714

AC:

6138

ExAC

AF:

0.695

AC:

84320

Asia WGS

AF:

0.579

AC:

2017

AN:

3478

EpiCase

AF:

0.716

EpiControl

AF:

0.716

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 29, 2020	This variant is associated with the following publications: (PMID: 17903293) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

T;.;T;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.50

T;T;T;T

MetaRNN

Benign

0.0000014

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L;.;L

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.6

N;N;N;D

REVEL

Benign

0.15

Sift

Uncertain

0.027

D;T;D;D

Sift4G

Benign

0.14

T;T;.;T

Polyphen

0.80

P;.;.;D

Vest4

0.024

MPC

0.065

ClinPred

0.0083

GERP RS

0.26

Varity_R

0.059

gMVP

0.14

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