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

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

2

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

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
MPDZNM_001378778.1 linkc.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
MPDZENST00000319217.12 linkc.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.:
32
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:
19
AN:
22
Hom.:
8
Cov.:
0
AF XY:
0.813
AC XY:
13
AN XY:
16
show subpopulations
African (AFR)
AC:
0
AN:
0
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AC:
0
AN:
0
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.864
AC:
19
AN:
22
Other (OTH)
AC:
0
AN:
0
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
0
1
1
2
2
3
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.:
32
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
0
1635
3270
4905
6540
8175
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
704
1408
2112
2816
3520
<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:
0.495
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
DANN
Benign
0.68
PhyloP100
-1.9
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs10809907; hg19: chr9-13134432; COSMIC: COSV59925190; COSMIC: COSV59925190; API