9-13115423-T-G

Variant names:

• chr9-13115423-T-G
• rs2274647
• NM_001378778.1:c.5380-89A>C

Variant summary

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

The NM_001378778.1(MPDZ):​c.5380-89A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,069,934 control chromosomes in the GnomAD database, including 63,824 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 0.34 (8972 hom., cov: 32)
  • Exomes 𝑓: 0.34 (54852 hom.)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.814
• 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: 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDZ	NM_001378778.1	MANE Select	c.5380-89A>C		intron	N/A	NP_001365707.1
	MPDZ	NM_001375413.1		c.5479-89A>C		intron	N/A	NP_001362342.1
	MPDZ	NM_001330637.2		c.5380-89A>C		intron	N/A	NP_001317566.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPDZ	ENST00000319217.12	TSL:5 MANE Select	c.5380-89A>C		intron	N/A	ENSP00000320006.7
	MPDZ	ENST00000541718.5	TSL:1	c.5380-1402A>C		intron	N/A	ENSP00000439807.1
	MPDZ	ENST00000447879.6	TSL:1	c.5281-89A>C		intron	N/A	ENSP00000415208.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50891 AN: 151906 Hom.: 8968 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.335 AC: 307703 AN: 917910 Hom.: 54852 AF XY: 0.343 AC XY: 161517 AN XY: 470884

African (AFR) AF: 0.365 AC: 8088 AN: 22166

American (AMR) AF: 0.265 AC: 9090 AN: 34360

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 7618 AN: 21334

East Asian (EAS) AF: 0.627 AC: 21400 AN: 34118

South Asian (SAS) AF: 0.521 AC: 35880 AN: 68848

European-Finnish (FIN) AF: 0.342 AC: 16000 AN: 46848

Middle Eastern (MID) AF: 0.299 AC: 1404 AN: 4698

European-Non Finnish (NFE) AF: 0.302 AC: 194064 AN: 643394

Other (OTH) AF: 0.336 AC: 14159 AN: 42144

GnomAD4 genome AF: 0.335 AC: 50931 AN: 152024 Hom.: 8972 Cov.: 32 AF XY: 0.339 AC XY: 25181 AN XY: 74300

African (AFR) AF: 0.360 AC: 14925 AN: 41470

American (AMR) AF: 0.283 AC: 4324 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1227 AN: 3470

East Asian (EAS) AF: 0.607 AC: 3128 AN: 5156

South Asian (SAS) AF: 0.527 AC: 2535 AN: 4814

European-Finnish (FIN) AF: 0.334 AC: 3526 AN: 10550

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20336 AN: 67968

Other (OTH) AF: 0.318 AC: 670 AN: 2106

Alfa AF: 0.306 Hom.: 13822

Bravo AF: 0.327

Asia WGS AF: 0.549 AC: 1907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.7
DANN	Benign	0.82
PhyloP100		0.81
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: rs2274647; hg19: chr9-13115422;