9-13106336-G-A

Position:

• chr9-13106336-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.*629C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,904 control chromosomes in the GnomAD database, including 10,126 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 0.36 (10126 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MPDZ NM_001378778.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.*629C>T		3_prime_UTR_variant	47/47	ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.*629C>T		3_prime_UTR_variant	47/47	5	NM_001378778.1	ENSP00000320006	A1
MPDZ	ENST00000541718.5	c.*629C>T		3_prime_UTR_variant	46/46	1		ENSP00000439807
MPDZ	ENST00000381017.6	n.2402C>T		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55056 AN: 151786 Hom.: 10116 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.389

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.363 AC: 55096 AN: 151904 Hom.: 10126 Cov.: 32 AF XY: 0.361 AC XY: 26802 AN XY: 74222

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.387

Alfa AF: 0.356 Hom.: 12912

Bravo AF: 0.376

Asia WGS AF: 0.440 AC: 1529 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.47

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: rs722651; hg19: chr9-13106335;