Genetic Variant MPDZ:c.2932-113G>A (chr9-13175988-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001378778.1(MPDZ):c.2932-113G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,432,966 control chromosomes in the GnomAD database, including 58,791 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.33 ( 8739 hom., cov: 32)

Exomes 𝑓: 0.27 ( 50052 hom. )

Consequence

MPDZ
NM_001378778.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1 link	c.2932-113G>A		intron_variant	Intron 20 of 46	ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12 link	c.2932-113G>A		intron_variant	Intron 20 of 46	5	NM_001378778.1	ENSP00000320006.7		O75970-1

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49577

AN:

151870

Hom.:

8722

Cov.:

show subpopulations

Gnomad AFR

AF:

0.448

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.334

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.478

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.316

GnomAD4 exome

AF:

0.274

AC:

351097

AN:

1280978

Hom.:

50052

Cov.:

AF XY:

0.275

AC XY:

172581

AN XY:

628182

show subpopulations

African (AFR)

AF:

0.464

AC:

12905

AN:

27806

American (AMR)

AF:

0.299

AC:

6547

AN:

21876

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

4043

AN:

20224

East Asian (EAS)

AF:

0.492

AC:

17219

AN:

35010

South Asian (SAS)

AF:

0.319

AC:

20543

AN:

64446

European-Finnish (FIN)

AF:

0.235

AC:

9454

AN:

40228

Middle Eastern (MID)

AF:

0.278

AC:

1461

AN:

5254

European-Non Finnish (NFE)

AF:

0.260

AC:

263710

AN:

1012656

Other (OTH)

AF:

0.285

AC:

15215

AN:

53478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

12615

25230

37845

50460

63075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9272

18544

27816

37088

46360

<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:

0.327

AC:

49653

AN:

151988

Hom.:

8739

Cov.:

AF XY:

0.328

AC XY:

24349

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.449

AC:

18588

AN:

41438

American (AMR)

AF:

0.334

AC:

5106

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

658

AN:

3468

East Asian (EAS)

AF:

0.478

AC:

2462

AN:

5146

South Asian (SAS)

AF:

0.320

AC:

1542

AN:

4820

European-Finnish (FIN)

AF:

0.242

AC:

2554

AN:

10566

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.260

AC:

17657

AN:

67950

Other (OTH)

AF:

0.319

AC:

675

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1650

3300

4949

6599

8249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

484

968

1452

1936

2420

<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:

0.224

Hom.:

678

Bravo

AF:

0.337

Asia WGS

AF:

0.423

AC:

1469

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.9

(source)

DANN

Benign

0.77

PhyloP100

-1.2

PromoterAI

0.014

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over