9-13176313-C-T

Variant names:

• chr9-13176313-C-T
• rs2274856
• NM_001378778.1:c.2754G>A

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.2754G>A​(p.Ser918Ser) 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:4
• Conservation: PhyloP100: -1.52
• Publications: 21 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=-0.8).
• BP6: Variant 9-13176313-C-T is Benign according to our data. Variant chr9-13176313-C-T is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.2754G>A	p.Ser918Ser	synonymous_variant	Exon 20 of 47	ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.2754G>A	p.Ser918Ser	synonymous_variant	Exon 20 of 47	5	NM_001378778.1	ENSP00000320006.7

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

GnomAD2 exomes AF: 0.289 AC: 69352 AN: 240034 AF XY: 0.285

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 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

African (AFR) AF: 0.485 AC: 16220 AN: 33416

American (AMR) AF: 0.281 AC: 12373 AN: 44042

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 5220 AN: 25992

East Asian (EAS) AF: 0.486 AC: 19144 AN: 39416

South Asian (SAS) AF: 0.316 AC: 26920 AN: 85276

European-Finnish (FIN) AF: 0.229 AC: 12200 AN: 53160

Middle Eastern (MID) AF: 0.278 AC: 1597 AN: 5754

European-Non Finnish (NFE) AF: 0.256 AC: 284048 AN: 1108634

Other (OTH) AF: 0.282 AC: 16960 AN: 60154

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

African (AFR) AF: 0.468 AC: 19355 AN: 41400

American (AMR) AF: 0.330 AC: 5036 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 657 AN: 3466

East Asian (EAS) AF: 0.477 AC: 2461 AN: 5154

South Asian (SAS) AF: 0.318 AC: 1534 AN: 4826

European-Finnish (FIN) AF: 0.237 AC: 2495 AN: 10542

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17429 AN: 67962

Other (OTH) AF: 0.321 AC: 677 AN: 2110

Alfa AF: 0.270 Hom.: 9522

Bravo AF: 0.340

Asia WGS AF: 0.421 AC: 1462 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 15, 2020

GeneDx

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.76
DANN	Benign	0.29
PhyloP100		-1.5
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: rs2274856; hg19: chr9-13176312; COSMIC: COSV59915709; COSMIC: COSV59915709;