rs7024892

Positions:

• chr9-13147724-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.3631-66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,242,426 control chromosomes in the GnomAD database, including 86,760 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 0.46 (18959 hom., cov: 32)
  • Exomes 𝑓: 0.34 (67801 hom.)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPDZ	NM_001378778.1	c.3631-66A>G		intron_variant		ENST00000319217.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPDZ	ENST00000319217.12	c.3631-66A>G		intron_variant		5	NM_001378778.1	A1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69558 AN: 151732 Hom.: 18907 Cov.: 32

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.438

GnomAD4 exome AF: 0.337 AC: 367415 AN: 1090574 Hom.: 67801 AF XY: 0.340 AC XY: 188470 AN XY: 554936

Gnomad4 AFR exome AF: 0.773

Gnomad4 AMR exome AF: 0.350

Gnomad4 ASJ exome AF: 0.308

Gnomad4 EAS exome AF: 0.495

Gnomad4 SAS exome AF: 0.453

Gnomad4 FIN exome AF: 0.254

Gnomad4 NFE exome AF: 0.309

Gnomad4 OTH exome AF: 0.363

GnomAD4 genome AF: 0.459 AC: 69667 AN: 151852 Hom.: 18959 Cov.: 32 AF XY: 0.457 AC XY: 33907 AN XY: 74218

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.440

Alfa AF: 0.376 Hom.: 2940

Bravo AF: 0.479

Asia WGS AF: 0.515 AC: 1788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	15
DANN	Benign	0.78

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: rs7024892; hg19: chr9-13147723; COSMIC: COSV59923467;