9-13115423-T-G

Position:

• chr9-13115423-T-G

Variant summary

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

The NM_001378778.1(MPDZ):​c.5380-89A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,069,934 control chromosomes in the GnomAD database, including 63,824 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 0.34 (8972 hom., cov: 32)
  • Exomes 𝑓: 0.34 (54852 hom.)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.814

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.5380-89A>C		intron_variant		ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.5380-89A>C		intron_variant		5	NM_001378778.1	ENSP00000320006.7

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50891 AN: 151906 Hom.: 8968 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.335 AC: 307703 AN: 917910 Hom.: 54852 AF XY: 0.343 AC XY: 161517 AN XY: 470884

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.627

Gnomad4 SAS exome AF: 0.521

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.302

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.335 AC: 50931 AN: 152024 Hom.: 8972 Cov.: 32 AF XY: 0.339 AC XY: 25181 AN XY: 74300

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.318

Alfa AF: 0.300 Hom.: 9655

Bravo AF: 0.327

Asia WGS AF: 0.549 AC: 1907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.7
DANN	Benign	0.82

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: rs2274647; hg19: chr9-13115422;