rs16930134

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.4810A>G(p.Thr1604Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,601,152 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 55 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 56 hom. )

Consequence

MPDZ
NM_001378778.1 missense, splice_region

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.487

Publications

1 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=0.0017824173).

BP6

Variant 9-13123296-T-C is Benign according to our data. Variant chr9-13123296-T-C is described in ClinVar as Benign. ClinVar VariationId is 211517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0519 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.4810A>G	p.Thr1604Ala	missense splice_region	Exon 36 of 47	NP_001365707.1
MPDZ	NM_001375413.1		c.4909A>G	p.Thr1637Ala	missense splice_region	Exon 37 of 48	NP_001362342.1
MPDZ	NM_001330637.2		c.4810A>G	p.Thr1604Ala	missense splice_region	Exon 36 of 47	NP_001317566.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MPDZ	ENST00000319217.12	TSL:5 MANE Select	c.4810A>G	p.Thr1604Ala	missense splice_region	Exon 36 of 47	ENSP00000320006.7
MPDZ	ENST00000541718.5	TSL:1	c.4810A>G	p.Thr1604Ala	missense splice_region	Exon 36 of 46	ENSP00000439807.1
MPDZ	ENST00000447879.6	TSL:1	c.4711A>G	p.Thr1571Ala	missense splice_region	Exon 35 of 46	ENSP00000415208.1

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2337

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0539

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00391

AC:

885

AN:

226152

AF XY:

0.00291

show subpopulations

Gnomad AFR exome

AF:

0.0577

Gnomad AMR exome

AF:

0.00258

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000992

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00148

AC:

2139

AN:

1448940

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

873

AN XY:

719540

show subpopulations

African (AFR)

AF:

0.0527

AC:

1747

AN:

33134

American (AMR)

AF:

0.00271

AC:

117

AN:

43112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25754

East Asian (EAS)

AF:

0.00

AC:

AN:

39082

South Asian (SAS)

AF:

0.0000832

AC:

AN:

84136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52786

Middle Eastern (MID)

AF:

0.00128

AC:

AN:

5486

European-Non Finnish (NFE)

AF:

0.0000624

AC:

AN:

1105486

Other (OTH)

AF:

0.00320

AC:

192

AN:

59964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

100

200

301

401

501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.0154

AC:

2338

AN:

152212

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1067

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0538

AC:

2233

AN:

41520

American (AMR)

AF:

0.00530

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68020

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

118

236

353

471

589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00623

Hom.:

Bravo

AF:

0.0173

ESP6500AA

AF:

0.0513

AC:

190

ESP6500EA

AF:

0.000488

AC:

ExAC

AF:

0.00449

AC:

542

Asia WGS

AF:

0.00173

AC:

AN:

3478

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

0.075

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.036

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

0.49

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.3

REVEL

Benign

0.013

Sift

Benign

0.079

Sift4G

Benign

0.57

Polyphen

0.017

Vest4

0.091

MVP

0.31

ClinPred

0.0098

GERP RS

0.48

Varity_R

0.066

gMVP

0.32

Mutation Taster

=61/39

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over