rs3765550

Positions:

• chr9-13108795-T-C

Variant summary

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

The NM_001378778.1(MPDZ):​c.6066+141A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 721,076 control chromosomes in the GnomAD database, including 63,168 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 0.35 (10565 hom., cov: 32)
  • Exomes 𝑓: 0.42 (52603 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]

MPDZ (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.6066+141A>G		intron_variant		ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.6066+141A>G		intron_variant		5	NM_001378778.1	ENSP00000320006.7

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53849 AN: 151926 Hom.: 10558 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.383

GnomAD4 exome AF: 0.424 AC: 241151 AN: 569032 Hom.: 52603 AF XY: 0.422 AC XY: 119122 AN XY: 281982

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.417

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.385

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.372

Gnomad4 NFE exome AF: 0.445

Gnomad4 OTH exome AF: 0.402

GnomAD4 genome AF: 0.354 AC: 53866 AN: 152044 Hom.: 10565 Cov.: 32 AF XY: 0.352 AC XY: 26126 AN XY: 74298

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.382

Alfa AF: 0.428 Hom.: 28984

Bravo AF: 0.350

Asia WGS AF: 0.326 AC: 1137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.85

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: rs3765550; hg19: chr9-13108794; COSMIC: COSV59916299;