rs16930194

Variant names:

• chr9-13192025-G-A
• rs16930194
• NM_001378778.1:c.1968+106C>T

Variant summary

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

The NM_001378778.1(MPDZ):​c.1968+106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 991,604 control chromosomes in the GnomAD database, including 1,426 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 0.070 (658 hom., cov: 32)
  • Exomes 𝑓: 0.034 (768 hom.)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 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.1968+106C>T		intron	N/A	NP_001365707.1	O75970-1
	MPDZ	NM_001375413.1		c.1968+106C>T		intron	N/A	NP_001362342.1
	MPDZ	NM_001330637.2		c.1968+106C>T		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.1968+106C>T		intron	N/A	ENSP00000320006.7	O75970-1
	MPDZ	ENST00000541718.5	TSL:1	c.1968+106C>T		intron	N/A	ENSP00000439807.1	O75970-2
	MPDZ	ENST00000447879.6	TSL:1	c.1968+106C>T		intron	N/A	ENSP00000415208.1	O75970-3

Frequencies

GnomAD3 genomes AF: 0.0700 AC: 10642 AN: 152078 Hom.: 657 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0474

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.00556

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0339

Gnomad OTH AF: 0.0660

GnomAD4 exome AF: 0.0341 AC: 28653 AN: 839408 Hom.: 768 AF XY: 0.0334 AC XY: 13698 AN XY: 409872

African (AFR) AF: 0.163 AC: 2987 AN: 18270

American (AMR) AF: 0.0394 AC: 490 AN: 12422

Ashkenazi Jewish (ASJ) AF: 0.0640 AC: 887 AN: 13864

East Asian (EAS) AF: 0.0000351 AC: 1 AN: 28460

South Asian (SAS) AF: 0.0141 AC: 358 AN: 25376

European-Finnish (FIN) AF: 0.00667 AC: 246 AN: 36868

Middle Eastern (MID) AF: 0.0369 AC: 146 AN: 3956

European-Non Finnish (NFE) AF: 0.0332 AC: 22007 AN: 663486

Other (OTH) AF: 0.0417 AC: 1531 AN: 36706

GnomAD4 genome AF: 0.0700 AC: 10651 AN: 152196 Hom.: 658 Cov.: 32 AF XY: 0.0666 AC XY: 4956 AN XY: 74406

African (AFR) AF: 0.171 AC: 7104 AN: 41486

American (AMR) AF: 0.0473 AC: 722 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0616 AC: 214 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4826

European-Finnish (FIN) AF: 0.00556 AC: 59 AN: 10616

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0339 AC: 2306 AN: 68022

Other (OTH) AF: 0.0653 AC: 138 AN: 2114

Alfa AF: 0.0593 Hom.: 107

Bravo AF: 0.0781

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.57
PhyloP100		0.064
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: rs16930194; hg19: chr9-13192024;