9-13176313-C-T

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.2754G>A(p.Ser918=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,607,748 control chromosomes in the GnomAD database, including 64,830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S918S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.33 (9008 hom., cov: 32)
  • Exomes 𝑓: 0.27 (55822 hom.)
• Consequence: MPDZ NM_001378778.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.52

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=-0.8).
• BP6: Variant 9-13176313-C-T is Benign according to our data. Variant chr9-13176313-C-T is described in ClinVar as [Benign]. Clinvar id is 158890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.52 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPDZ	NM_001378778.1	c.2754G>A	p.Ser918=	synonymous_variant	20/47	ENST00000319217.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPDZ	ENST00000319217.12	c.2754G>A	p.Ser918=	synonymous_variant	20/47	5	NM_001378778.1	A1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49969 AN: 151786 Hom.: 8982 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.318

GnomAD3 exomes AF: 0.289 AC: 69352 AN: 240034 Hom.: 10738 AF XY: 0.285 AC XY: 37073 AN XY: 129930

Gnomad AFR exome AF: 0.474

Gnomad AMR exome AF: 0.277

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.464

Gnomad SAS exome AF: 0.314

Gnomad FIN exome AF: 0.231

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.263

GnomAD4 exome AF: 0.271 AC: 394682 AN: 1455844 Hom.: 55822 Cov.: 35 AF XY: 0.272 AC XY: 196603 AN XY: 723622

Gnomad4 AFR exome AF: 0.485

Gnomad4 AMR exome AF: 0.281

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.486

Gnomad4 SAS exome AF: 0.316

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.330 AC: 50057 AN: 151904 Hom.: 9008 Cov.: 32 AF XY: 0.330 AC XY: 24511 AN XY: 74220

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.321

Alfa AF: 0.261 Hom.: 7113

Bravo AF: 0.340

Asia WGS AF: 0.421 AC: 1462 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 15, 2020	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 08, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.76
Dann	Benign	0.29

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: rs2274856; hg19: chr9-13176312; COSMIC: COSV59915709; COSMIC: COSV59915709;