9-13163011-G-C

Variant names:

• chr9-13163011-G-C
• rs1331672
• NM_001378778.1:c.3255-216C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378778.1(MPDZ):​c.3255-216C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,924 control chromosomes in the GnomAD database, including 13,432 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (13432 hom., cov: 33)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.3255-216C>G		intron_variant	Intron 22 of 46	ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.3255-216C>G		intron_variant	Intron 22 of 46	5	NM_001378778.1	ENSP00000320006.7

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60483 AN: 151808 Hom.: 13418 Cov.: 33

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.401

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.399 AC: 60545 AN: 151924 Hom.: 13432 Cov.: 33 AF XY: 0.394 AC XY: 29284 AN XY: 74236

African (AFR) AF: 0.598 AC: 24773 AN: 41426

American (AMR) AF: 0.398 AC: 6071 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 986 AN: 3466

East Asian (EAS) AF: 0.472 AC: 2424 AN: 5138

South Asian (SAS) AF: 0.331 AC: 1594 AN: 4820

European-Finnish (FIN) AF: 0.225 AC: 2377 AN: 10574

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.309 AC: 20998 AN: 67932

Other (OTH) AF: 0.403 AC: 851 AN: 2112

Alfa AF: 0.358 Hom.: 1304

Bravo AF: 0.418

Asia WGS AF: 0.426 AC: 1474 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.72
DANN	Benign	0.64
PhyloP100		-1.3
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: rs1331672; hg19: chr9-13163010; COSMIC: COSV59923784;