dbSNP rs7024892: MPDZ:c.3631-66A>G (chr9-13147724-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.3631-66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,242,426 control chromosomes in the GnomAD database, including 86,760 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 0.46 ( 18959 hom., cov: 32)

Exomes 𝑓: 0.34 ( 67801 hom. )

Consequence

MPDZ
NM_001378778.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.258

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=-0.77).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1 link	c.3631-66A>G		intron_variant	Intron 25 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.3631-66A>G		intron_variant	Intron 25 of 46	5	NM_001378778.1	ENSP00000320006.7		O75970-1

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

69558

AN:

151732

Hom.:

18907

Cov.:

show subpopulations

Gnomad AFR

AF:

0.763

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.424

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.487

Gnomad SAS

AF:

0.460

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.438

GnomAD4 exome

AF:

0.337

AC:

367415

AN:

1090574

Hom.:

67801

AF XY:

0.340

AC XY:

188470

AN XY:

554936

show subpopulations

African (AFR)

AF:

0.773

AC:

19356

AN:

25044

American (AMR)

AF:

0.350

AC:

13379

AN:

38214

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

6625

AN:

21502

East Asian (EAS)

AF:

0.495

AC:

18544

AN:

37456

South Asian (SAS)

AF:

0.453

AC:

32273

AN:

71264

European-Finnish (FIN)

AF:

0.254

AC:

12906

AN:

50734

Middle Eastern (MID)

AF:

0.390

AC:

1900

AN:

4878

European-Non Finnish (NFE)

AF:

0.309

AC:

245223

AN:

794054

Other (OTH)

AF:

0.363

AC:

17209

AN:

47428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

11225

22451

33676

44902

56127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7218

14436

21654

28872

36090

<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:

0.459

AC:

69667

AN:

151852

Hom.:

18959

Cov.:

AF XY:

0.457

AC XY:

33907

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.764

AC:

31646

AN:

41440

American (AMR)

AF:

0.424

AC:

6439

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

1032

AN:

3466

East Asian (EAS)

AF:

0.487

AC:

2504

AN:

5144

South Asian (SAS)

AF:

0.460

AC:

2214

AN:

4814

European-Finnish (FIN)

AF:

0.258

AC:

2722

AN:

10564

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.319

AC:

21685

AN:

67910

Other (OTH)

AF:

0.440

AC:

927

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1617

3234

4852

6469

8086

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.372

Hom.:

4560

Bravo

AF:

0.479

Asia WGS

AF:

0.515

AC:

1788

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

0.26

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