NM_001378778.1:c.1804-26G>C

Variant names:

• chr9-13192321-C-G
• rs1331676
• NM_001378778.1:c.1804-26G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378778.1(MPDZ):​c.1804-26G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,567,236 control chromosomes in the GnomAD database, including 770,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73592 hom., cov: 32)
  • Exomes 𝑓: 0.99 (696937 hom.)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0450
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-13192321-C-G is Benign according to our data. Variant chr9-13192321-C-G is described in ClinVar as Benign. ClinVar VariationId is 1321175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.1804-26G>C		intron_variant	Intron 14 of 46	ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.1804-26G>C		intron_variant	Intron 14 of 46	5	NM_001378778.1	ENSP00000320006.7

Frequencies

GnomAD3 genomes AF: 0.983 AC: 149539 AN: 152156 Hom.: 73532 Cov.: 32

Gnomad AFR AF: 0.955

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.922

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.981

GnomAD2 exomes AF: 0.983 AC: 183932 AN: 187116 AF XY: 0.980

Gnomad AFR exome AF: 0.952

Gnomad AMR exome AF: 0.991

Gnomad ASJ exome AF: 0.993

Gnomad EAS exome AF: 0.997

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.997

Gnomad OTH exome AF: 0.987

GnomAD4 exome AF: 0.992 AC: 1404019 AN: 1414962 Hom.: 696937 Cov.: 28 AF XY: 0.990 AC XY: 693059 AN XY: 699900

African (AFR) AF: 0.951 AC: 30928 AN: 32510

American (AMR) AF: 0.991 AC: 37675 AN: 38002

Ashkenazi Jewish (ASJ) AF: 0.994 AC: 25192 AN: 25334

East Asian (EAS) AF: 0.998 AC: 37833 AN: 37906

South Asian (SAS) AF: 0.923 AC: 74265 AN: 80470

European-Finnish (FIN) AF: 1.00 AC: 50824 AN: 50834

Middle Eastern (MID) AF: 0.974 AC: 5542 AN: 5688

European-Non Finnish (NFE) AF: 0.998 AC: 1083828 AN: 1085600

Other (OTH) AF: 0.988 AC: 57932 AN: 58618

GnomAD4 genome AF: 0.983 AC: 149658 AN: 152274 Hom.: 73592 Cov.: 32 AF XY: 0.982 AC XY: 73102 AN XY: 74458

African (AFR) AF: 0.955 AC: 39664 AN: 41542

American (AMR) AF: 0.992 AC: 15154 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 3448 AN: 3472

East Asian (EAS) AF: 0.996 AC: 5151 AN: 5174

South Asian (SAS) AF: 0.922 AC: 4447 AN: 4824

European-Finnish (FIN) AF: 1.00 AC: 10630 AN: 10630

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67885 AN: 68028

Other (OTH) AF: 0.982 AC: 2077 AN: 2116

Alfa AF: 0.993 Hom.: 8482

Bravo AF: 0.983

Asia WGS AF: 0.952 AC: 3310 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hydrocephalus, nonsyndromic, autosomal recessive 2 Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		0.045
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: rs1331676; hg19: chr9-13192320;