9-13108795-T-C

Variant names:

• chr9-13108795-T-C
• rs3765550
• NM_001378778.1:c.6066+141A>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.6066+141A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 721,076 control chromosomes in the GnomAD database, including 63,168 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 0.35 (10565 hom., cov: 32)
  • Exomes 𝑓: 0.42 (52603 hom.)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• 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=-0.47).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.6066+141A>G		intron_variant	Intron 46 of 46	ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.6066+141A>G		intron_variant	Intron 46 of 46	5	NM_001378778.1	ENSP00000320006.7

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53849 AN: 151926 Hom.: 10558 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.424 AC: 241151 AN: 569032 Hom.: 52603 AF XY: 0.422 AC XY: 119122 AN XY: 281982

African (AFR) AF: 0.161 AC: 2128 AN: 13210

American (AMR) AF: 0.417 AC: 3982 AN: 9540

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 4337 AN: 10668

East Asian (EAS) AF: 0.385 AC: 9069 AN: 23562

South Asian (SAS) AF: 0.259 AC: 3722 AN: 14344

European-Finnish (FIN) AF: 0.372 AC: 11716 AN: 31514

Middle Eastern (MID) AF: 0.388 AC: 865 AN: 2230

European-Non Finnish (NFE) AF: 0.445 AC: 194846 AN: 437888

Other (OTH) AF: 0.402 AC: 10486 AN: 26076

GnomAD4 genome AF: 0.354 AC: 53866 AN: 152044 Hom.: 10565 Cov.: 32 AF XY: 0.352 AC XY: 26126 AN XY: 74298

African (AFR) AF: 0.170 AC: 7078 AN: 41530

American (AMR) AF: 0.408 AC: 6230 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1463 AN: 3464

East Asian (EAS) AF: 0.360 AC: 1861 AN: 5164

South Asian (SAS) AF: 0.295 AC: 1421 AN: 4816

European-Finnish (FIN) AF: 0.390 AC: 4118 AN: 10556

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30280 AN: 67936

Other (OTH) AF: 0.382 AC: 806 AN: 2112

Alfa AF: 0.417 Hom.: 57653

Bravo AF: 0.350

Asia WGS AF: 0.326 AC: 1137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.85
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: rs3765550; hg19: chr9-13108794; COSMIC: COSV59916299;