rs17273542

Positions:

Variant summary

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

The NM_001378778.1(MPDZ):c.275C>T(p.Ser92Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00963 in 1,612,678 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. S92S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0081 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0098 ( 99 hom. )

Consequence

MPDZ
NM_001378778.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.73

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=0.0025561154).

BP6

Variant 9-13224492-G-A is Benign according to our data. Variant chr9-13224492-G-A is described in ClinVar as [Benign]. Clinvar id is 774428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00813 (1237/152146) while in subpopulation NFE AF= 0.0118 (804/67974). AF 95% confidence interval is 0.0111. There are 11 homozygotes in gnomad4. There are 562 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPDZ	NM_001378778.1 linkuse as main transcript	c.275C>T	p.Ser92Leu	missense_variant	4/47	ENST00000319217.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPDZ	ENST00000319217.12 linkuse as main transcript	c.275C>T	p.Ser92Leu	missense_variant	4/47	5	NM_001378778.1	A1	O75970-1

Frequencies

GnomAD3 genomes

AF:

0.00814

AC:

1237

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00295

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00787

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00790

AC:

1961

AN:

248256

Hom.:

AF XY:

0.00853

AC XY:

1149

AN XY:

134694

show subpopulations

Gnomad AFR exome

AF:

0.00201

Gnomad AMR exome

AF:

0.00655

Gnomad ASJ exome

AF:

0.0244

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00624

Gnomad FIN exome

AF:

0.000557

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.00997

GnomAD4 exome

AF:

0.00979

AC:

14300

AN:

1460532

Hom.:

Cov.:

AF XY:

0.00973

AC XY:

7072

AN XY:

726580

show subpopulations

Gnomad4 AFR exome

AF:

0.00177

Gnomad4 AMR exome

AF:

0.00707

Gnomad4 ASJ exome

AF:

0.0261

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00622

Gnomad4 FIN exome

AF:

0.000637

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.00897

GnomAD4 genome

AF:

0.00813

AC:

1237

AN:

152146

Hom.:

Cov.:

AF XY:

0.00755

AC XY:

562

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00294

Gnomad4 AMR

AF:

0.00786

Gnomad4 ASJ

AF:

0.0314

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0101

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.0118

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.00831

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.00296

AC:

ESP6500EA

AF:

0.0126

AC:

103

ExAC

AF:

0.00824

AC:

995

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0113

EpiControl

AF:

0.0142

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	MPDZ: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 13, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.087

T;.;.;.;.;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.87

D;D;D;D;.;D

MetaRNN

Benign

0.0026

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L;L;L;L;.

MutationTaster

Benign

0.65

N;N;N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.6

D;D;D;D;D;D

REVEL

Benign

0.095

Sift

Benign

0.15

T;T;T;T;T;T

Sift4G

Benign

0.11

T;T;T;T;T;T

Polyphen

0.0090, 0.041

.;B;B;.;B;.

Vest4

0.085

MVP

0.23

ClinPred

0.024

GERP RS

3.0

Varity_R

0.062

gMVP

0.38

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