rs3264

Variant names:

• chr9-13106599-T-C
• rs3264
• NM_001378778.1:c.*366A>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.*366A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 164,138 control chromosomes in the GnomAD database, including 11,351 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 0.37 (10453 hom., cov: 30)
  • Exomes 𝑓: 0.36 (898 hom.)
• Consequence: MPDZ NM_001378778.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146
• Publications: 16 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.*366A>G		3_prime_UTR_variant	Exon 47 of 47	ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.*366A>G		3_prime_UTR_variant	Exon 47 of 47	5	NM_001378778.1	ENSP00000320006.7

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55639 AN: 151654 Hom.: 10445 Cov.: 30

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.365 AC: 4509 AN: 12366 Hom.: 898 Cov.: 0 AF XY: 0.365 AC XY: 2297 AN XY: 6300

African (AFR) AF: 0.344 AC: 191 AN: 556

American (AMR) AF: 0.353 AC: 135 AN: 382

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 190 AN: 550

East Asian (EAS) AF: 0.132 AC: 93 AN: 704

South Asian (SAS) AF: 0.295 AC: 33 AN: 112

European-Finnish (FIN) AF: 0.381 AC: 179 AN: 470

Middle Eastern (MID) AF: 0.400 AC: 24 AN: 60

European-Non Finnish (NFE) AF: 0.387 AC: 3355 AN: 8670

Other (OTH) AF: 0.358 AC: 309 AN: 862

GnomAD4 genome AF: 0.367 AC: 55681 AN: 151772 Hom.: 10453 Cov.: 30 AF XY: 0.369 AC XY: 27359 AN XY: 74152

African (AFR) AF: 0.340 AC: 14059 AN: 41348

American (AMR) AF: 0.385 AC: 5872 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1206 AN: 3470

East Asian (EAS) AF: 0.156 AC: 800 AN: 5144

South Asian (SAS) AF: 0.243 AC: 1169 AN: 4808

European-Finnish (FIN) AF: 0.482 AC: 5063 AN: 10496

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26207 AN: 67936

Other (OTH) AF: 0.352 AC: 742 AN: 2108

Alfa AF: 0.380 Hom.: 18644

Bravo AF: 0.359

Asia WGS AF: 0.254 AC: 881 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.9
DANN	Benign	0.84
PhyloP100		-0.15
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: rs3264; hg19: chr9-13106598;