rs4740548

Variant names:

Variant summary

Our verdict is Benign. Variant got -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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E702K) has been classified as Likely 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

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 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=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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1 link	c.2105A>T	p.Glu702Val	missense_variant	Exon 16 of 47	ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12 link	c.2105A>T	p.Glu702Val	missense_variant	Exon 16 of 47	5	NM_001378778.1	ENSP00000320006.7		O75970-1

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

GnomAD3 exomes

AF:

0.0189

AC:

4692

AN:

248086

Hom.:

138

AF XY:

0.0220

AC XY:

2959

AN XY:

134598

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 SAS exome

AF:

0.0840

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

Gnomad4 AFR exome

AF:

0.0338

Gnomad4 AMR exome

AF:

0.0113

Gnomad4 ASJ exome

AF:

0.0106

Gnomad4 EAS exome

AF:

0.00192

Gnomad4 SAS exome

AF:

0.0799

Gnomad4 FIN exome

AF:

0.000956

Gnomad4 NFE exome

AF:

0.00808

Gnomad4 OTH exome

AF:

0.0169

GnomAD4 genome

AF:

0.0171

AC:

2608

AN:

152266

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

1343

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0329

Gnomad4 AMR

AF:

0.0116

Gnomad4 ASJ

AF:

0.0132

Gnomad4 EAS

AF:

0.00463

Gnomad4 SAS

AF:

0.0804

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00814

Gnomad4 OTH

AF:

0.0223

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29924831) -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;.;.;.;.;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

D;D;D;D;.;D

MetaRNN

Benign

0.0046

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L;L;L;L;.

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.7

D;D;D;D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0040

D;D;D;D;D;D

Sift4G

Uncertain

0.030

D;D;D;D;D;D

Polyphen

0.99, 0.96

.;D;D;.;D;.

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

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