rs10809907

chr9-13134433-C-Gchr9-13134433-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.4384-529G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,008 control chromosomes in the GnomAD database, including 25,305 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 0.54 (25297 hom., cov: 32)
  • Exomes 𝑓: 0.86 (8 hom.)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPDZ	NM_001378778.1	c.4384-529G>C		intron_variant		ENST00000319217.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPDZ	ENST00000319217.12	c.4384-529G>C		intron_variant		5	NM_001378778.1	A1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82592 AN: 151870 Hom.: 25299 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.560

GnomAD4 exome AF: 0.864 AC: 19 AN: 22 Hom.: 8 Cov.: 0 AF XY: 0.813 AC XY: 13 AN XY: 16

Gnomad4 NFE exome AF: 0.864

GnomAD4 genome AF: 0.543 AC: 82598 AN: 151986 Hom.: 25297 Cov.: 32 AF XY: 0.545 AC XY: 40474 AN XY: 74262

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.743

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.557

Alfa AF: 0.495 Hom.: 1667

Bravo AF: 0.523

Asia WGS AF: 0.481 AC: 1674 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.36
Dann	Benign	0.68

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: rs10809907; hg19: chr9-13134432; COSMIC: COSV59925190; COSMIC: COSV59925190;