rs76115127

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378778.1(MPDZ):c.3893C>T(p.Pro1298Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,613,254 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 70 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 73 hom. )

Consequence

MPDZ
NM_001378778.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.91

Publications

1 publications found

Variant links:

Genes affected

MPDZ (HGNC:7208): (multiple PDZ domain crumbs cell polarity complex component) The protein encoded by this gene has multiple PDZ domains, which are hallmarks of protein-protein interactions. The encoded protein is known to interact with the HTR2C receptor and may cause it to clump at the cell surface. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

MPDZ Gene-Disease associations (from GenCC):

hydrocephalus, nonsyndromic, autosomal recessive 2
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

MPDZ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002631098).

BP6

Variant 9-13140097-G-A is Benign according to our data. Variant chr9-13140097-G-A is described in ClinVar as Benign. ClinVar VariationId is 211513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0514 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378778.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MPDZ	NM_001378778.1	MANE Select	c.3893C>T	p.Pro1298Leu	missense	Exon 28 of 47	NP_001365707.1
MPDZ	NM_001375413.1		c.3893C>T	p.Pro1298Leu	missense	Exon 28 of 48	NP_001362342.1
MPDZ	NM_001330637.2		c.3893C>T	p.Pro1298Leu	missense	Exon 28 of 47	NP_001317566.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MPDZ	ENST00000319217.12	TSL:5 MANE Select	c.3893C>T	p.Pro1298Leu	missense	Exon 28 of 47	ENSP00000320006.7
MPDZ	ENST00000541718.5	TSL:1	c.3893C>T	p.Pro1298Leu	missense	Exon 28 of 46	ENSP00000439807.1
MPDZ	ENST00000447879.6	TSL:1	c.3794C>T	p.Pro1265Leu	missense	Exon 27 of 46	ENSP00000415208.1

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2344

AN:

151586

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0532

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00782

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00910

GnomAD2 exomes

AF:

0.00366

AC:

911

AN:

248816

AF XY:

0.00266

show subpopulations

Gnomad AFR exome

AF:

0.0530

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000444

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00154

AC:

2257

AN:

1461550

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

980

AN XY:

727068

show subpopulations

African (AFR)

AF:

0.0580

AC:

1942

AN:

33466

American (AMR)

AF:

0.00253

AC:

113

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1111766

Other (OTH)

AF:

0.00292

AC:

176

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

118

236

355

473

591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.0155

AC:

2349

AN:

151704

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

1130

AN XY:

74086

show subpopulations

African (AFR)

AF:

0.0532

AC:

2201

AN:

41360

American (AMR)

AF:

0.00781

AC:

119

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5012

South Asian (SAS)

AF:

0.000208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

67978

Other (OTH)

AF:

0.00900

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

111

222

332

443

554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00632

Hom.:

Bravo

AF:

0.0168

ESP6500AA

AF:

0.0491

AC:

195

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00453

AC:

548

Asia WGS

AF:

0.00173

AC:

AN:

3476

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

Apr 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MPDZ-related disorder

Benign:1

Sep 06, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.15

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.23

PhyloP100

1.9

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.030

Sift

Benign

0.058

Sift4G

Benign

0.18

Polyphen

0.0080

Vest4

0.27

MVP

0.36

ClinPred

0.011

GERP RS

3.0

Varity_R

0.043

gMVP

0.52

Mutation Taster

=92/8

polymorphism

(source)

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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over