rs13297480

Variant names:

• chr9-13219571-T-C
• rs13297480
• NM_001378778.1:c.1074A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001378778.1(MPDZ):​c.1074A>G​(p.Thr358Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,611,318 control chromosomes in the GnomAD database, including 16,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1728 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14279 hom.)
• Consequence: MPDZ NM_001378778.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.54
• Publications: 8 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 9-13219571-T-C is Benign according to our data. Variant chr9-13219571-T-C is described in ClinVar as Benign. ClinVar VariationId is 158889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.54 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 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.1074A>G	p.Thr358Thr	synonymous	Exon 8 of 47	NP_001365707.1	O75970-1
	MPDZ	NM_001375413.1		c.1074A>G	p.Thr358Thr	synonymous	Exon 8 of 48	NP_001362342.1
	MPDZ	NM_001330637.2		c.1074A>G	p.Thr358Thr	synonymous	Exon 8 of 47	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.1074A>G	p.Thr358Thr	synonymous	Exon 8 of 47	ENSP00000320006.7	O75970-1
	MPDZ	ENST00000541718.5	TSL:1	c.1074A>G	p.Thr358Thr	synonymous	Exon 8 of 46	ENSP00000439807.1	O75970-2
	MPDZ	ENST00000447879.6	TSL:1	c.1074A>G	p.Thr358Thr	synonymous	Exon 8 of 46	ENSP00000415208.1	O75970-3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21949 AN: 151814 Hom.: 1728 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.00680

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.163

GnomAD2 exomes AF: 0.123 AC: 30452 AN: 247348 AF XY: 0.125

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.0769

Gnomad ASJ exome AF: 0.136

Gnomad EAS exome AF: 0.00465

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.137 AC: 199396 AN: 1459386 Hom.: 14279 Cov.: 32 AF XY: 0.136 AC XY: 98859 AN XY: 725920

African (AFR) AF: 0.168 AC: 5600 AN: 33378

American (AMR) AF: 0.0803 AC: 3573 AN: 44512

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3408 AN: 26022

East Asian (EAS) AF: 0.00321 AC: 127 AN: 39590

South Asian (SAS) AF: 0.118 AC: 10181 AN: 86168

European-Finnish (FIN) AF: 0.151 AC: 8063 AN: 53250

Middle Eastern (MID) AF: 0.201 AC: 1154 AN: 5750

European-Non Finnish (NFE) AF: 0.143 AC: 159033 AN: 1110498

Other (OTH) AF: 0.137 AC: 8257 AN: 60218

GnomAD4 genome AF: 0.145 AC: 21962 AN: 151932 Hom.: 1728 Cov.: 32 AF XY: 0.146 AC XY: 10806 AN XY: 74242

African (AFR) AF: 0.166 AC: 6897 AN: 41502

American (AMR) AF: 0.128 AC: 1945 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3468

East Asian (EAS) AF: 0.00662 AC: 34 AN: 5136

South Asian (SAS) AF: 0.118 AC: 570 AN: 4820

European-Finnish (FIN) AF: 0.162 AC: 1718 AN: 10600

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9836 AN: 67880

Other (OTH) AF: 0.161 AC: 339 AN: 2110

Alfa AF: 0.144 Hom.: 1687

Bravo AF: 0.139

Asia WGS AF: 0.0800 AC: 277 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Hydrocephalus, nonsyndromic, autosomal recessive 2 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0070
DANN	Benign	0.32
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs13297480; hg19: chr9-13219570; COSMIC: COSV59941940;