Genetic Variant MPDZ:c.6066+141A>G (chr9-13108795-T-C) – 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.6066+141A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 721,076 control chromosomes in the GnomAD database, including 63,168 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 0.35 ( 10565 hom., cov: 32)

Exomes 𝑓: 0.42 ( 52603 hom. )

Consequence

MPDZ
NM_001378778.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0640

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=-0.47).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1 link	c.6066+141A>G		intron_variant	Intron 46 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.6066+141A>G		intron_variant	Intron 46 of 46	5	NM_001378778.1	ENSP00000320006.7		O75970-1

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53849

AN:

151926

Hom.:

10558

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.531

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.360

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.383

GnomAD4 exome

AF:

0.424

AC:

241151

AN:

569032

Hom.:

52603

AF XY:

0.422

AC XY:

119122

AN XY:

281982

show subpopulations

African (AFR)

AF:

0.161

AC:

2128

AN:

13210

American (AMR)

AF:

0.417

AC:

3982

AN:

9540

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

4337

AN:

10668

East Asian (EAS)

AF:

0.385

AC:

9069

AN:

23562

South Asian (SAS)

AF:

0.259

AC:

3722

AN:

14344

European-Finnish (FIN)

AF:

0.372

AC:

11716

AN:

31514

Middle Eastern (MID)

AF:

0.388

AC:

865

AN:

2230

European-Non Finnish (NFE)

AF:

0.445

AC:

194846

AN:

437888

Other (OTH)

AF:

0.402

AC:

10486

AN:

26076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6629

13257

19886

26514

33143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5438

10876

16314

21752

27190

<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:

0.354

AC:

53866

AN:

152044

Hom.:

10565

Cov.:

AF XY:

0.352

AC XY:

26126

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.170

AC:

7078

AN:

41530

American (AMR)

AF:

0.408

AC:

6230

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

1463

AN:

3464

East Asian (EAS)

AF:

0.360

AC:

1861

AN:

5164

South Asian (SAS)

AF:

0.295

AC:

1421

AN:

4816

European-Finnish (FIN)

AF:

0.390

AC:

4118

AN:

10556

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.446

AC:

30280

AN:

67936

Other (OTH)

AF:

0.382

AC:

806

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1708

3416

5125

6833

8541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<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:

0.417

Hom.:

57653

Bravo

AF:

0.350

Asia WGS

AF:

0.326

AC:

1137

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.064

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