rs3264

Positions:

• chr9-13106599-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378778.1(MPDZ):​c.*366A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 164,138 control chromosomes in the GnomAD database, including 11,351 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 0.37 (10453 hom., cov: 30)
  • Exomes 𝑓: 0.36 (898 hom.)
• Consequence: MPDZ NM_001378778.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPDZ	NM_001378778.1	c.*366A>G		3_prime_UTR_variant	47/47	ENST00000319217.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPDZ	ENST00000319217.12	c.*366A>G		3_prime_UTR_variant	47/47	5	NM_001378778.1	A1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55639 AN: 151654 Hom.: 10445 Cov.: 30

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.365 AC: 4509 AN: 12366 Hom.: 898 Cov.: 0 AF XY: 0.365 AC XY: 2297 AN XY: 6300

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.353

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.295

Gnomad4 FIN exome AF: 0.381

Gnomad4 NFE exome AF: 0.387

Gnomad4 OTH exome AF: 0.358

GnomAD4 genome AF: 0.367 AC: 55681 AN: 151772 Hom.: 10453 Cov.: 30 AF XY: 0.369 AC XY: 27359 AN XY: 74152

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.352

Alfa AF: 0.379 Hom.: 14725

Bravo AF: 0.359

Asia WGS AF: 0.254 AC: 881 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.9
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs3264; hg19: chr9-13106598;