rs2039333

Positions:

• chr9-13205265-G-A
• chr9-13205265-G-C

Variant summary

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

The NM_001378778.1(MPDZ):​c.1475-158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 152,220 control chromosomes in the GnomAD database, including 67,417 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 0.94 (67417 hom., cov: 32)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPDZ	NM_001378778.1	c.1475-158C>T		intron_variant		ENST00000319217.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPDZ	ENST00000319217.12	c.1475-158C>T		intron_variant		5	NM_001378778.1	A1

Frequencies

GnomAD3 genomes AF: 0.938 AC: 142600 AN: 152102 Hom.: 67379 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.973

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.915

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.947

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.937 AC: 142690 AN: 152220 Hom.: 67417 Cov.: 32 AF XY: 0.938 AC XY: 69839 AN XY: 74416

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.973

Gnomad4 ASJ AF: 0.977

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.991

Gnomad4 OTH AF: 0.947

Alfa AF: 0.966 Hom.: 15825

Bravo AF: 0.931

Asia WGS AF: 0.939 AC: 3264 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.99
DANN	Benign	0.49

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: rs2039333; hg19: chr9-13205264;