9-13175988-C-T

Variant summary

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

The NM_001378778.1(MPDZ):c.2932-113G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,432,966 control chromosomes in the GnomAD database, including 58,791 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 0.33 (8739 hom., cov: 32)
  • Exomes 𝑓: 0.27 (50052 hom.)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPDZ	NM_001378778.1	c.2932-113G>A		intron_variant		ENST00000319217.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPDZ	ENST00000319217.12	c.2932-113G>A		intron_variant		5	NM_001378778.1	A1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49577 AN: 151870 Hom.: 8722 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.316

GnomAD4 exome AF: 0.274 AC: 351097 AN: 1280978 Hom.: 50052 Cov.: 22 AF XY: 0.275 AC XY: 172581 AN XY: 628182

Gnomad4 AFR exome AF: 0.464

Gnomad4 AMR exome AF: 0.299

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.492

Gnomad4 SAS exome AF: 0.319

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.327 AC: 49653 AN: 151988 Hom.: 8739 Cov.: 32 AF XY: 0.328 AC XY: 24349 AN XY: 74284

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.319

Alfa AF: 0.215 Hom.: 591

Bravo AF: 0.337

Asia WGS AF: 0.423 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.9
Dann	Benign	0.77

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: rs1331674; hg19: chr9-13175987; COSMIC: COSV59923828; COSMIC: COSV59923828;