Variant rs34704118 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001378778.1(MPDZ):c.2580A>G(p.Leu860=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00582 in 1,612,418 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 39 hom. )

Consequence

MPDZ
NM_001378778.1 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -0.108

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 9-13183487-T-C is Benign according to our data. Variant chr9-13183487-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211510.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1, Likely_benign=1}.

BP7

Synonymous conserved (PhyloP=-0.108 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00404 (614/152084) while in subpopulation NFE AF= 0.00629 (427/67928). AF 95% confidence interval is 0.00579. There are 0 homozygotes in gnomad4. There are 284 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPDZ	NM_001378778.1 linkuse as main transcript	c.2580A>G	p.Leu860=	synonymous_variant	19/47	ENST00000319217.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPDZ	ENST00000319217.12 linkuse as main transcript	c.2580A>G	p.Leu860=	synonymous_variant	19/47	5	NM_001378778.1	A1	O75970-1

Frequencies

GnomAD3 genomes

AF:

0.00403

AC:

613

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00467

Gnomad ASJ

AF:

0.00894

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00629

Gnomad OTH

AF:

0.00671

GnomAD3 exomes

AF:

0.00440

AC:

1089

AN:

247636

Hom.:

AF XY:

0.00451

AC XY:

606

AN XY:

134346

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.00309

Gnomad ASJ exome

AF:

0.00918

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00334

Gnomad FIN exome

AF:

0.000559

Gnomad NFE exome

AF:

0.00644

Gnomad OTH exome

AF:

0.00634

GnomAD4 exome

AF:

0.00600

AC:

8767

AN:

1460334

Hom.:

Cov.:

AF XY:

0.00594

AC XY:

4318

AN XY:

726430

show subpopulations

Gnomad4 AFR exome

AF:

0.000928

Gnomad4 AMR exome

AF:

0.00350

Gnomad4 ASJ exome

AF:

0.00851

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00354

Gnomad4 FIN exome

AF:

0.000769

Gnomad4 NFE exome

AF:

0.00680

Gnomad4 OTH exome

AF:

0.00650

GnomAD4 genome

AF:

0.00404

AC:

614

AN:

152084

Hom.:

Cov.:

AF XY:

0.00382

AC XY:

284

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00466

Gnomad4 ASJ

AF:

0.00894

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00629

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00470

Hom.:

Bravo

AF:

0.00487

Asia WGS

AF:

0.00144

AC:

AN:

3476

EpiCase

AF:

0.00873

EpiControl

AF:

0.00667

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	MPDZ: BP4, BP7 -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 29, 2014

- -

MPDZ-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 18, 2019

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.2

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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