rs4740548

Variant names:

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.2105A>T(p.Glu702Val) variant causes a missense change. The variant allele was found at a frequency of 0.0134 in 1,613,010 control chromosomes in the GnomAD database, including 510 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E702K) has been classified as Benign.

Frequency

Genomes: 𝑓 0.017 ( 51 hom., cov: 32)

Exomes 𝑓: 0.013 ( 459 hom. )

Consequence

MPDZ
NM_001378778.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.79

Publications

7 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=0.0045934916).

BP6

Variant 9-13190163-T-A is Benign according to our data. Variant chr9-13190163-T-A is described in ClinVar as Benign. ClinVar VariationId is 211509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0738 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.2105A>T	p.Glu702Val	missense	Exon 16 of 47	NP_001365707.1
MPDZ	NM_001375413.1		c.2105A>T	p.Glu702Val	missense	Exon 16 of 48	NP_001362342.1
MPDZ	NM_001330637.2		c.2105A>T	p.Glu702Val	missense	Exon 16 of 47	NP_001317566.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MPDZ	ENST00000319217.12	TSL:5 MANE Select	c.2105A>T	p.Glu702Val	missense	Exon 16 of 47	ENSP00000320006.7
MPDZ	ENST00000541718.5	TSL:1	c.2105A>T	p.Glu702Val	missense	Exon 16 of 46	ENSP00000439807.1
MPDZ	ENST00000447879.6	TSL:1	c.2105A>T	p.Glu702Val	missense	Exon 16 of 46	ENSP00000415208.1

Frequencies

GnomAD3 genomes

AF:

0.0172

AC:

2610

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0330

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.00482

Gnomad SAS

AF:

0.0803

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00814

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.0189

AC:

4692

AN:

248086

AF XY:

0.0220

show subpopulations

Gnomad AFR exome

AF:

0.0318

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.00286

Gnomad FIN exome

AF:

0.000558

Gnomad NFE exome

AF:

0.00856

Gnomad OTH exome

AF:

0.0178

GnomAD4 exome

AF:

0.0131

AC:

19083

AN:

1460744

Hom.:

459

Cov.:

AF XY:

0.0152

AC XY:

11019

AN XY:

726596

show subpopulations

African (AFR)

AF:

0.0338

AC:

1131

AN:

33438

American (AMR)

AF:

0.0113

AC:

506

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.0106

AC:

276

AN:

26112

East Asian (EAS)

AF:

0.00192

AC:

AN:

39562

South Asian (SAS)

AF:

0.0799

AC:

6874

AN:

86062

European-Finnish (FIN)

AF:

0.000956

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.0295

AC:

170

AN:

5760

European-Non Finnish (NFE)

AF:

0.00808

AC:

8980

AN:

1111468

Other (OTH)

AF:

0.0169

AC:

1019

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

897

1794

2692

3589

4486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.0171

AC:

2608

AN:

152266

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

1343

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0329

AC:

1365

AN:

41550

American (AMR)

AF:

0.0116

AC:

177

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0132

AC:

AN:

3472

East Asian (EAS)

AF:

0.00463

AC:

AN:

5180

South Asian (SAS)

AF:

0.0804

AC:

387

AN:

4816

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00814

AC:

554

AN:

68020

Other (OTH)

AF:

0.0223

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

119

239

358

478

597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.00470

Hom.:

Bravo

AF:

0.0172

ExAC

AF:

0.0207

AC:

2508

Asia WGS

AF:

0.0470

AC:

165

AN:

3476

EpiCase

AF:

0.0117

EpiControl

AF:

0.0111

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

5.8

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.28

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.030

Polyphen

0.99

Vest4

0.40

ClinPred

0.044

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.55

Mutation Taster

=99/1

polymorphism (auto)

(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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over