9-13105639-T-C

Variant names:

• chr9-13105639-T-C
• rs10733253
• NM_001378778.1:c.*1326A>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.*1326A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,174 control chromosomes in the GnomAD database, including 56,364 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 0.85 (56364 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MPDZ NM_001378778.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 3 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=-0.59).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378778.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDZ	NM_001378778.1	MANE Select	c.*1326A>G		downstream_gene	N/A	NP_001365707.1
	MPDZ	NM_001375413.1		c.*1326A>G		downstream_gene	N/A	NP_001362342.1
	MPDZ	NM_001330637.2		c.*1326A>G		downstream_gene	N/A	NP_001317566.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDZ	ENST00000319217.12	TSL:5 MANE Select	c.*1326A>G		downstream_gene	N/A	ENSP00000320006.7
	MPDZ	ENST00000541718.5	TSL:1	c.*1326A>G		downstream_gene	N/A	ENSP00000439807.1
	MPDZ	ENST00000381017.6	TSL:2	n.*67A>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129860 AN: 152056 Hom.: 56358 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.949

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.942

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.854 AC: 129910 AN: 152174 Hom.: 56364 Cov.: 32 AF XY: 0.855 AC XY: 63629 AN XY: 74408

African (AFR) AF: 0.690 AC: 28617 AN: 41474

American (AMR) AF: 0.824 AC: 12601 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3183 AN: 3466

East Asian (EAS) AF: 0.852 AC: 4401 AN: 5168

South Asian (SAS) AF: 0.839 AC: 4046 AN: 4824

European-Finnish (FIN) AF: 0.949 AC: 10070 AN: 10610

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.942 AC: 64050 AN: 68026

Other (OTH) AF: 0.875 AC: 1849 AN: 2112

Alfa AF: 0.916 Hom.: 111085

Bravo AF: 0.839

Asia WGS AF: 0.797 AC: 2770 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		1.9
Mutation Taster		=99/1	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10733253; hg19: chr9-13105638;