9-13125202-T-C

Variant names:

• chr9-13125202-T-C
• rs2297003
• NM_001378778.1:c.4807+14A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378778.1(MPDZ):​c.4807+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,572,996 control chromosomes in the GnomAD database, including 357,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (29317 hom., cov: 31)
  • Exomes 𝑓: 0.68 (328030 hom.)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.840
• Publications: 6 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-13125202-T-C is Benign according to our data. Variant chr9-13125202-T-C is described in ClinVar as Benign. ClinVar VariationId is 211516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.4807+14A>G		intron_variant	Intron 35 of 46	ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.4807+14A>G		intron_variant	Intron 35 of 46	5	NM_001378778.1	ENSP00000320006.7

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92801 AN: 151640 Hom.: 29308 Cov.: 31

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.621

GnomAD2 exomes AF: 0.662 AC: 148699 AN: 224604 AF XY: 0.666

Gnomad AFR exome AF: 0.442

Gnomad AMR exome AF: 0.681

Gnomad ASJ exome AF: 0.704

Gnomad EAS exome AF: 0.540

Gnomad FIN exome AF: 0.747

Gnomad NFE exome AF: 0.694

Gnomad OTH exome AF: 0.681

GnomAD4 exome AF: 0.677 AC: 962277 AN: 1421238 Hom.: 328030 Cov.: 32 AF XY: 0.677 AC XY: 475340 AN XY: 702388

African (AFR) AF: 0.448 AC: 14557 AN: 32488

American (AMR) AF: 0.675 AC: 28160 AN: 41736

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 16433 AN: 23396

East Asian (EAS) AF: 0.519 AC: 20402 AN: 39294

South Asian (SAS) AF: 0.641 AC: 51272 AN: 80032

European-Finnish (FIN) AF: 0.746 AC: 38805 AN: 52032

Middle Eastern (MID) AF: 0.671 AC: 2988 AN: 4456

European-Non Finnish (NFE) AF: 0.689 AC: 750893 AN: 1089342

Other (OTH) AF: 0.663 AC: 38767 AN: 58462

GnomAD4 genome AF: 0.612 AC: 92845 AN: 151758 Hom.: 29317 Cov.: 31 AF XY: 0.614 AC XY: 45490 AN XY: 74140

African (AFR) AF: 0.450 AC: 18607 AN: 41360

American (AMR) AF: 0.611 AC: 9323 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2486 AN: 3470

East Asian (EAS) AF: 0.532 AC: 2708 AN: 5094

South Asian (SAS) AF: 0.641 AC: 3083 AN: 4812

European-Finnish (FIN) AF: 0.742 AC: 7806 AN: 10514

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.689 AC: 46809 AN: 67946

Other (OTH) AF: 0.618 AC: 1302 AN: 2108

Alfa AF: 0.651 Hom.: 11360

Bravo AF: 0.597

Asia WGS AF: 0.548 AC: 1910 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Apr 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hydrocephalus, nonsyndromic, autosomal recessive 2 Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.53
PhyloP100		-0.84
Mutation Taster		=99/1	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

Other links and lift over

dbSNP: rs2297003; hg19: chr9-13125201;