Genetic Variant NM_001378778.1:c.4384-529G>C (chr9-13134433-C-G) – 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.4384-529G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,008 control chromosomes in the GnomAD database, including 25,305 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 0.54 ( 25297 hom., cov: 32)

Exomes 𝑓: 0.86 ( 8 hom. )

Consequence

MPDZ
NM_001378778.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.91

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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1 link	c.4384-529G>C		intron_variant	Intron 31 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.4384-529G>C		intron_variant	Intron 31 of 46	5	NM_001378778.1	ENSP00000320006.7		O75970-1

Frequencies

GnomAD3 genomes

AF:

0.544

AC:

82592

AN:

151870

Hom.:

25299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.566

Gnomad AMR

AF:

0.575

Gnomad ASJ

AF:

0.699

Gnomad EAS

AF:

0.515

Gnomad SAS

AF:

0.540

Gnomad FIN

AF:

0.743

Gnomad MID

AF:

0.650

Gnomad NFE

AF:

0.682

Gnomad OTH

AF:

0.560

GnomAD4 exome

AF:

0.864

AC:

AN:

Hom.:

Cov.:

AF XY:

0.813

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.864

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.543

AC:

82598

AN:

151986

Hom.:

25297

Cov.:

AF XY:

0.545

AC XY:

40474

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.242

AC:

10023

AN:

41422

American (AMR)

AF:

0.575

AC:

8783

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.699

AC:

2424

AN:

3470

East Asian (EAS)

AF:

0.515

AC:

2662

AN:

5166

South Asian (SAS)

AF:

0.540

AC:

2603

AN:

4822

European-Finnish (FIN)

AF:

0.743

AC:

7834

AN:

10542

Middle Eastern (MID)

AF:

0.644

AC:

188

AN:

292

European-Non Finnish (NFE)

AF:

0.682

AC:

46389

AN:

67982

Other (OTH)

AF:

0.557

AC:

1176

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1635

3270

4905

6540

8175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.495

Hom.:

1667

Bravo

AF:

0.523

Asia WGS

AF:

0.481

AC:

1674

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.36

(source)

DANN

Benign

0.68

PhyloP100

-1.9

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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NM_001378778.1:c.4384-529G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over