9-13235288-A-T

Variant names:

• chr9-13235288-A-T
• rs1389752
• NM_001378778.1:c.184-10705T>A

Variant summary

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

The NM_001378778.1(MPDZ):​c.184-10705T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,122 control chromosomes in the GnomAD database, including 52,540 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 0.83 (52540 hom., cov: 33)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.827
• Publications: 2 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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.184-10705T>A		intron_variant	Intron 3 of 46	ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.184-10705T>A		intron_variant	Intron 3 of 46	5	NM_001378778.1	ENSP00000320006.7

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125802 AN: 152004 Hom.: 52504 Cov.: 33

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.874

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.828 AC: 125890 AN: 152122 Hom.: 52540 Cov.: 33 AF XY: 0.827 AC XY: 61508 AN XY: 74370

African (AFR) AF: 0.721 AC: 29935 AN: 41508

American (AMR) AF: 0.865 AC: 13214 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.874 AC: 3031 AN: 3466

East Asian (EAS) AF: 0.993 AC: 5134 AN: 5172

South Asian (SAS) AF: 0.893 AC: 4306 AN: 4822

European-Finnish (FIN) AF: 0.838 AC: 8872 AN: 10588

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58593 AN: 67972

Other (OTH) AF: 0.831 AC: 1754 AN: 2110

Alfa AF: 0.837 Hom.: 6263

Bravo AF: 0.829

Asia WGS AF: 0.918 AC: 3190 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		0.83
Mutation Taster		=99/1	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: rs1389752; hg19: chr9-13235287;