Genetic Variant NM_001378778.1:c.3055+33_3055+35delCTC (chr9-13175716-TGAG-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001378778.1(MPDZ):c.3055+33_3055+35delCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 1,549,384 control chromosomes in the GnomAD database, including 340,926 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 25219 hom., cov: 0)

Exomes 𝑓: 0.66 ( 315707 hom. )

Consequence

MPDZ
NM_001378778.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.576

Publications

6 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1 link	c.3055+33_3055+35delCTC		intron_variant	Intron 21 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.3055+33_3055+35delCTC		intron_variant	Intron 21 of 46	5	NM_001378778.1	ENSP00000320006.7		O75970-1

Frequencies

GnomAD3 genomes

AF:

0.526

AC:

79767

AN:

151572

Hom.:

25220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.611

Gnomad AMR

AF:

0.580

Gnomad ASJ

AF:

0.708

Gnomad EAS

AF:

0.508

Gnomad SAS

AF:

0.554

Gnomad FIN

AF:

0.752

Gnomad MID

AF:

0.666

Gnomad NFE

AF:

0.692

Gnomad OTH

AF:

0.552

GnomAD2 exomes

AF:

0.618

AC:

106126

AN:

171724

AF XY:

0.621

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.652

Gnomad ASJ exome

AF:

0.692

Gnomad EAS exome

AF:

0.510

Gnomad FIN exome

AF:

0.751

Gnomad NFE exome

AF:

0.680

Gnomad OTH exome

AF:

0.653

GnomAD4 exome

AF:

0.664

AC:

928153

AN:

1397696

Hom.:

315707

AF XY:

0.662

AC XY:

457479

AN XY:

690720

show subpopulations

African (AFR)

AF:

0.133

AC:

4325

AN:

32488

American (AMR)

AF:

0.647

AC:

23607

AN:

36500

Ashkenazi Jewish (ASJ)

AF:

0.697

AC:

17506

AN:

25130

East Asian (EAS)

AF:

0.500

AC:

18642

AN:

37308

South Asian (SAS)

AF:

0.557

AC:

44241

AN:

79434

European-Finnish (FIN)

AF:

0.755

AC:

37591

AN:

49760

Middle Eastern (MID)

AF:

0.620

AC:

3510

AN:

5658

European-Non Finnish (NFE)

AF:

0.691

AC:

741896

AN:

1073356

Other (OTH)

AF:

0.634

AC:

36835

AN:

58062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

12323

24646

36968

49291

61614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18866

37732

56598

75464

94330

<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:

0.526

AC:

79770

AN:

151688

Hom.:

25219

Cov.:

AF XY:

0.529

AC XY:

39204

AN XY:

74102

show subpopulations

African (AFR)

AF:

0.157

AC:

6510

AN:

41470

American (AMR)

AF:

0.580

AC:

8826

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.708

AC:

2454

AN:

3464

East Asian (EAS)

AF:

0.509

AC:

2605

AN:

5122

South Asian (SAS)

AF:

0.553

AC:

2655

AN:

4804

European-Finnish (FIN)

AF:

0.752

AC:

7912

AN:

10526

Middle Eastern (MID)

AF:

0.664

AC:

194

AN:

292

European-Non Finnish (NFE)

AF:

0.692

AC:

46904

AN:

67786

Other (OTH)

AF:

0.550

AC:

1160

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1496

2992

4487

5983

7479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<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:

0.624

Hom.:

5740

Bravo

AF:

0.503

Asia WGS

AF:

0.491

AC:

1710

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.58

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over