rs3831219

Variant names:

• chr9-13175716-TGAG-T
• rs3831219
• NM_001378778.1:c.3055+33_3055+35delCTC

Your query was ambiguous. Multiple possible variants found:

• chr9-13175716-TGAG-T
• chr9-13175716-TGAG-TGAGGAG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001378778.1(MPDZ):​c.3055+33_3055+35delCTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 1,549,384 control chromosomes in the GnomAD database, including 340,926 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (25219 hom., cov: 0)
  • Exomes 𝑓: 0.66 (315707 hom.)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576
• Publications: 6 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: Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDZ	NM_001378778.1	MANE Select	c.3055+33_3055+35delCTC		intron	N/A	NP_001365707.1	O75970-1
	MPDZ	NM_001375413.1		c.3055+33_3055+35delCTC		intron	N/A	NP_001362342.1
	MPDZ	NM_001330637.2		c.3055+33_3055+35delCTC		intron	N/A	NP_001317566.1	O75970-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDZ	ENST00000319217.12	TSL:5 MANE Select	c.3055+33_3055+35delCTC		intron	N/A	ENSP00000320006.7	O75970-1
	MPDZ	ENST00000541718.5	TSL:1	c.3055+33_3055+35delCTC		intron	N/A	ENSP00000439807.1	O75970-2
	MPDZ	ENST00000447879.6	TSL:1	c.3055+33_3055+35delCTC		intron	N/A	ENSP00000415208.1	O75970-3

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79767 AN: 151572 Hom.: 25220 Cov.: 0

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.552

GnomAD2 exomes AF: 0.618 AC: 106126 AN: 171724 AF XY: 0.621

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.652

Gnomad ASJ exome AF: 0.692

Gnomad EAS exome AF: 0.510

Gnomad FIN exome AF: 0.751

Gnomad NFE exome AF: 0.680

Gnomad OTH exome AF: 0.653

GnomAD4 exome AF: 0.664 AC: 928153 AN: 1397696 Hom.: 315707 AF XY: 0.662 AC XY: 457479 AN XY: 690720

African (AFR) AF: 0.133 AC: 4325 AN: 32488

American (AMR) AF: 0.647 AC: 23607 AN: 36500

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 17506 AN: 25130

East Asian (EAS) AF: 0.500 AC: 18642 AN: 37308

South Asian (SAS) AF: 0.557 AC: 44241 AN: 79434

European-Finnish (FIN) AF: 0.755 AC: 37591 AN: 49760

Middle Eastern (MID) AF: 0.620 AC: 3510 AN: 5658

European-Non Finnish (NFE) AF: 0.691 AC: 741896 AN: 1073356

Other (OTH) AF: 0.634 AC: 36835 AN: 58062

GnomAD4 genome AF: 0.526 AC: 79770 AN: 151688 Hom.: 25219 Cov.: 0 AF XY: 0.529 AC XY: 39204 AN XY: 74102

African (AFR) AF: 0.157 AC: 6510 AN: 41470

American (AMR) AF: 0.580 AC: 8826 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2454 AN: 3464

East Asian (EAS) AF: 0.509 AC: 2605 AN: 5122

South Asian (SAS) AF: 0.553 AC: 2655 AN: 4804

European-Finnish (FIN) AF: 0.752 AC: 7912 AN: 10526

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.692 AC: 46904 AN: 67786

Other (OTH) AF: 0.550 AC: 1160 AN: 2108

Alfa AF: 0.624 Hom.: 5740

Bravo AF: 0.503

Asia WGS AF: 0.491 AC: 1710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.58
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: rs3831219; hg19: chr9-13175715; COSMIC: COSV59915652;