NM_001378778.1:c.4341A>G

Variant names:

• chr9-13136134-T-C
• rs61753784
• NM_001378778.1:c.4341A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001378778.1(MPDZ):​c.4341A>G​(p.Val1447Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00624 in 1,613,018 control chromosomes in the GnomAD database, including 528 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (278 hom., cov: 31)
  • Exomes 𝑓: 0.0035 (250 hom.)
• Consequence: MPDZ NM_001378778.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.968
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-13136134-T-C is Benign according to our data. Variant chr9-13136134-T-C is described in ClinVar as Benign. ClinVar VariationId is 211514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.968 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378778.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDZ	NM_001378778.1	MANE Select	c.4341A>G	p.Val1447Val	synonymous	Exon 31 of 47	NP_001365707.1
	MPDZ	NM_001375413.1		c.4341A>G	p.Val1447Val	synonymous	Exon 31 of 48	NP_001362342.1
	MPDZ	NM_001330637.2		c.4341A>G	p.Val1447Val	synonymous	Exon 31 of 47	NP_001317566.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDZ	ENST00000319217.12	TSL:5 MANE Select	c.4341A>G	p.Val1447Val	synonymous	Exon 31 of 47	ENSP00000320006.7
	MPDZ	ENST00000541718.5	TSL:1	c.4341A>G	p.Val1447Val	synonymous	Exon 31 of 46	ENSP00000439807.1
	MPDZ	ENST00000447879.6	TSL:1	c.4242A>G	p.Val1414Val	synonymous	Exon 30 of 46	ENSP00000415208.1

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4937 AN: 152024 Hom.: 274 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0216

GnomAD2 exomes AF: 0.00804 AC: 1996 AN: 248212 AF XY: 0.00618

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.00572

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000515

Gnomad OTH exome AF: 0.00365

GnomAD4 exome AF: 0.00350 AC: 5115 AN: 1460876 Hom.: 250 Cov.: 29 AF XY: 0.00297 AC XY: 2157 AN XY: 726692

African (AFR) AF: 0.117 AC: 3893 AN: 33402

American (AMR) AF: 0.00687 AC: 307 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86142

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53344

Middle Eastern (MID) AF: 0.00676 AC: 39 AN: 5766

European-Non Finnish (NFE) AF: 0.000290 AC: 322 AN: 1111480

Other (OTH) AF: 0.00865 AC: 522 AN: 60344

GnomAD4 genome AF: 0.0326 AC: 4955 AN: 152142 Hom.: 278 Cov.: 31 AF XY: 0.0313 AC XY: 2328 AN XY: 74394

African (AFR) AF: 0.112 AC: 4645 AN: 41458

American (AMR) AF: 0.0140 AC: 214 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000676 AC: 46 AN: 68018

Other (OTH) AF: 0.0214 AC: 45 AN: 2106

Alfa AF: 0.0149 Hom.: 87

Bravo AF: 0.0372

Asia WGS AF: 0.00895 AC: 31 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.000892

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.69
PhyloP100		0.97
PromoterAI		0.012	Neutral
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

Other links and lift over

dbSNP: rs61753784; hg19: chr9-13136133;