rs16930194

Positions:

• chr9-13192025-G-A

Variant summary

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

The NM_001378778.1(MPDZ):​c.1968+106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 991,604 control chromosomes in the GnomAD database, including 1,426 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 0.070 (658 hom., cov: 32)
  • Exomes 𝑓: 0.034 (768 hom.)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.1968+106C>T		intron_variant		ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.1968+106C>T		intron_variant		5	NM_001378778.1	ENSP00000320006	A1

Frequencies

GnomAD3 genomes AF: 0.0700 AC: 10642 AN: 152078 Hom.: 657 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0474

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.00556

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0339

Gnomad OTH AF: 0.0660

GnomAD4 exome AF: 0.0341 AC: 28653 AN: 839408 Hom.: 768 AF XY: 0.0334 AC XY: 13698 AN XY: 409872

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.0394

Gnomad4 ASJ exome AF: 0.0640

Gnomad4 EAS exome AF: 0.0000351

Gnomad4 SAS exome AF: 0.0141

Gnomad4 FIN exome AF: 0.00667

Gnomad4 NFE exome AF: 0.0332

Gnomad4 OTH exome AF: 0.0417

GnomAD4 genome AF: 0.0700 AC: 10651 AN: 152196 Hom.: 658 Cov.: 32 AF XY: 0.0666 AC XY: 4956 AN XY: 74406

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0473

Gnomad4 ASJ AF: 0.0616

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.00556

Gnomad4 NFE AF: 0.0339

Gnomad4 OTH AF: 0.0653

Alfa AF: 0.0593 Hom.: 107

Bravo AF: 0.0781

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.57

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: rs16930194; hg19: chr9-13192024;