chr12-68302863-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001354969.2(MDM1):c.1759C>T(p.Arg587Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000645 in 1,255,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R587H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000065 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

MDM1
NM_001354969.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.322

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

MDM1 links:

ENSG00000303715 (HGNC:):

ENSG00000303715 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11483419).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354969.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MDM1	NM_001354969.2	MANE Select	c.1759C>T	p.Arg587Cys	missense	Exon 13 of 15	NP_001341898.1	A0A804HIJ5
MDM1	NM_017440.6		c.1729C>T	p.Arg577Cys	missense	Exon 12 of 14	NP_059136.2	Q8TC05-1
MDM1	NM_001205028.3		c.1624C>T	p.Arg542Cys	missense	Exon 12 of 14	NP_001191957.1	Q8TC05-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MDM1	ENST00000682720.1	MANE Select	c.1759C>T	p.Arg587Cys	missense	Exon 13 of 15	ENSP00000507100.1	A0A804HIJ5
MDM1	ENST00000303145.11	TSL:1	c.1729C>T	p.Arg577Cys	missense	Exon 12 of 14	ENSP00000302537.7	Q8TC05-1
MDM1	ENST00000540418.5	TSL:1	n.*1223C>T		non_coding_transcript_exon	Exon 11 of 13	ENSP00000443815.2	F5H804

Frequencies

GnomAD3 genomes

AF:

0.0000645

AC:

AN:

123952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000586

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000973

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000356

AC:

AN:

168576

AF XY:

0.0000532

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000585

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000645

AC:

AN:

1131278

Hom.:

Cov.:

AF XY:

0.0000595

AC XY:

AN XY:

554326

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25428

American (AMR)

AF:

0.00

AC:

AN:

23780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18112

East Asian (EAS)

AF:

0.0000360

AC:

AN:

27784

South Asian (SAS)

AF:

0.00

AC:

AN:

49982

European-Finnish (FIN)

AF:

0.0000256

AC:

AN:

39000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4238

European-Non Finnish (NFE)

AF:

0.0000779

AC:

AN:

898564

Other (OTH)

AF:

0.0000225

AC:

AN:

44390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000645

AC:

AN:

123952

Hom.:

Cov.:

AF XY:

0.0000872

AC XY:

AN XY:

57366

show subpopulations

African (AFR)

AF:

0.0000586

AC:

AN:

34102

American (AMR)

AF:

0.00

AC:

AN:

9742

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3306

East Asian (EAS)

AF:

0.00

AC:

AN:

4252

South Asian (SAS)

AF:

0.00

AC:

AN:

3788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

194

European-Non Finnish (NFE)

AF:

0.0000973

AC:

AN:

61672

Other (OTH)

AF:

0.00

AC:

AN:

1566

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000992

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.38

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.79

M_CAP

Benign

0.014

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

0.32

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.060

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.015

Polyphen

0.039

Vest4

0.14

MVP

0.30

MPC

0.33

ClinPred

0.26

GERP RS

3.6

PromoterAI

-0.017

Neutral

(source)

Varity_R

0.096

gMVP

0.17

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over