rs34605667

Positions:

chr9-13112025-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001378778.1(MPDZ):c.5723G>A(p.Arg1908Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0386 in 1,613,092 control chromosomes in the GnomAD database, including 1,421 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 111 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1310 hom. )

Consequence

MPDZ
NM_001378778.1 missense, splice_region

Scores

Splicing: ADA: 0.002675

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.62

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:

MPDZ (HGNC:):

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=0.005102515).

BP6

Variant 9-13112025-C-T is Benign according to our data. Variant chr9-13112025-C-T is described in ClinVar as [Benign]. Clinvar id is 211519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-13112025-C-T is described in Lovd as [Benign]. Variant chr9-13112025-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0306 (4665/152256) while in subpopulation NFE AF= 0.0445 (3027/68020). AF 95% confidence interval is 0.0432. There are 111 homozygotes in gnomad4. There are 2353 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 111 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPDZ	NM_001378778.1 linkuse as main transcript	c.5723G>A	p.Arg1908Lys	missense_variant, splice_region_variant	43/47	ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12 linkuse as main transcript	c.5723G>A	p.Arg1908Lys	missense_variant, splice_region_variant	43/47	5	NM_001378778.1	ENSP00000320006.7		O75970-1

Frequencies

GnomAD3 genomes

AF:

0.0307

AC:

4666

AN:

152138

Hom.:

111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00830

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0176

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.0743

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0445

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0328

AC:

8174

AN:

249038

Hom.:

167

AF XY:

0.0335

AC XY:

4527

AN XY:

135092

show subpopulations

Gnomad AFR exome

AF:

0.00646

Gnomad AMR exome

AF:

0.0153

Gnomad ASJ exome

AF:

0.0319

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.0140

Gnomad FIN exome

AF:

0.0727

Gnomad NFE exome

AF:

0.0442

Gnomad OTH exome

AF:

0.0402

GnomAD4 exome

AF:

0.0394

AC:

57521

AN:

1460836

Hom.:

1310

Cov.:

AF XY:

0.0388

AC XY:

28231

AN XY:

726700

show subpopulations

Gnomad4 AFR exome

AF:

0.00535

Gnomad4 AMR exome

AF:

0.0170

Gnomad4 ASJ exome

AF:

0.0325

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0152

Gnomad4 FIN exome

AF:

0.0720

Gnomad4 NFE exome

AF:

0.0435

Gnomad4 OTH exome

AF:

0.0352

GnomAD4 genome

AF:

0.0306

AC:

4665

AN:

152256

Hom.:

111

Cov.:

AF XY:

0.0316

AC XY:

2353

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00828

Gnomad4 AMR

AF:

0.0176

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.0743

Gnomad4 NFE

AF:

0.0445

Gnomad4 OTH

AF:

0.0241

Alfa

AF:

0.0388

Hom.:

207

Bravo

AF:

0.0262

TwinsUK

AF:

0.0437

AC:

162

ALSPAC

AF:

0.0462

AC:

178

ESP6500AA

AF:

0.00784

AC:

ESP6500EA

AF:

0.0402

AC:

332

ExAC

AF:

0.0331

AC:

3994

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.0406

EpiControl

AF:

0.0419

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 08, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.61

CADD

Uncertain

DANN

Benign

0.72

DEOGEN2

Benign

0.014

T;.;.;.;.;.;.;.;.

Eigen

Benign

-0.21

Eigen_PC

Benign

0.026

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.72

T;T;T;T;T;T;T;.;T

MetaRNN

Benign

0.0051

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.0

N;.;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.010

N;N;.;N;N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.66

T;T;.;T;T;T;T;T;T

Sift4G

Benign

0.95

T;T;T;T;T;T;T;T;T

Polyphen

0.033

B;P;B;.;.;B;.;B;.

Vest4

0.24

ClinPred

0.025

GERP RS

5.7

Varity_R

0.16

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0027

dbscSNV1_RF

Benign

0.096

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