rs13297480

Positions:

• chr9-13219571-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001378778.1(MPDZ):​c.1074A>G​(p.Thr358=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,611,318 control chromosomes in the GnomAD database, including 16,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1728 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14279 hom.)
• Consequence: MPDZ NM_001378778.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.54

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 9-13219571-T-C is Benign according to our data. Variant chr9-13219571-T-C is described in ClinVar as [Benign]. Clinvar id is 158889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.54 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.1074A>G	p.Thr358=	synonymous_variant	8/47	ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.1074A>G	p.Thr358=	synonymous_variant	8/47	5	NM_001378778.1	ENSP00000320006	A1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21949 AN: 151814 Hom.: 1728 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.00680

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.163

GnomAD3 exomes AF: 0.123 AC: 30452 AN: 247348 Hom.: 2155 AF XY: 0.125 AC XY: 16794 AN XY: 134232

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.0769

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.00465

Gnomad SAS exome AF: 0.120

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.137 AC: 199396 AN: 1459386 Hom.: 14279 Cov.: 32 AF XY: 0.136 AC XY: 98859 AN XY: 725920

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.0803

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.00321

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.145 AC: 21962 AN: 151932 Hom.: 1728 Cov.: 32 AF XY: 0.146 AC XY: 10806 AN XY: 74242

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.00662

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.161

Alfa AF: 0.144 Hom.: 1394

Bravo AF: 0.139

Asia WGS AF: 0.0800 AC: 277 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 05, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 08, 2013

- -

Hydrocephalus, nonsyndromic, autosomal recessive 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0070
DANN	Benign	0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs13297480; hg19: chr9-13219570; COSMIC: COSV59941940;