rs722651

Variant names:

• chr9-13106336-G-A
• rs722651
• NM_001378778.1:c.*629C>T

Variant summary

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

The NM_001378778.1(MPDZ):​c.*629C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,904 control chromosomes in the GnomAD database, including 10,126 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 0.36 (10126 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MPDZ NM_001378778.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.*629C>T		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.*629C>T		3_prime_UTR_variant	Exon 47 of 47	5	NM_001378778.1	ENSP00000320006.7

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55056 AN: 151786 Hom.: 10116 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.389

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.363 AC: 55096 AN: 151904 Hom.: 10126 Cov.: 32 AF XY: 0.361 AC XY: 26802 AN XY: 74222

African (AFR) AF: 0.368 AC: 15259 AN: 41430

American (AMR) AF: 0.418 AC: 6384 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1333 AN: 3466

East Asian (EAS) AF: 0.495 AC: 2560 AN: 5168

South Asian (SAS) AF: 0.388 AC: 1865 AN: 4810

European-Finnish (FIN) AF: 0.269 AC: 2831 AN: 10532

Middle Eastern (MID) AF: 0.434 AC: 126 AN: 290

European-Non Finnish (NFE) AF: 0.348 AC: 23605 AN: 67912

Other (OTH) AF: 0.387 AC: 818 AN: 2112

Alfa AF: 0.356 Hom.: 15450

Bravo AF: 0.376

Asia WGS AF: 0.440 AC: 1529 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.47
PhyloP100		-0.70
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: rs722651; hg19: chr9-13106335;