9-13115350-G-C

Position:

• chr9-13115350-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001378778.1(MPDZ):​c.5380-16C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 1,595,530 control chromosomes in the GnomAD database, including 31 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 0.0095 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (23 hom.)
• Consequence: MPDZ NM_001378778.1 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537

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=-0.85).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00947 (1441/152174) while in subpopulation AFR AF= 0.0249 (1035/41522). AF 95% confidence interval is 0.0237. There are 8 homozygotes in gnomad4. There are 671 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.5380-16C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.5380-16C>G		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001378778.1	ENSP00000320006	A1

Frequencies

GnomAD3 genomes AF: 0.00944 AC: 1436 AN: 152056 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00432

Gnomad OTH AF: 0.00865

GnomAD3 exomes AF: 0.00440 AC: 1054 AN: 239562 Hom.: 6 AF XY: 0.00404 AC XY: 532 AN XY: 131624

Gnomad AFR exome AF: 0.0267

Gnomad AMR exome AF: 0.00349

Gnomad ASJ exome AF: 0.00112

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00136

Gnomad FIN exome AF: 0.000513

Gnomad NFE exome AF: 0.00454

Gnomad OTH exome AF: 0.00304

GnomAD4 exome AF: 0.00467 AC: 6745 AN: 1443356 Hom.: 23 Cov.: 28 AF XY: 0.00445 AC XY: 3203 AN XY: 719144

Gnomad4 AFR exome AF: 0.0277

Gnomad4 AMR exome AF: 0.00384

Gnomad4 ASJ exome AF: 0.000923

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00150

Gnomad4 FIN exome AF: 0.000632

Gnomad4 NFE exome AF: 0.00468

Gnomad4 OTH exome AF: 0.00494

GnomAD4 genome AF: 0.00947 AC: 1441 AN: 152174 Hom.: 8 Cov.: 32 AF XY: 0.00902 AC XY: 671 AN XY: 74396

Gnomad4 AFR AF: 0.0249

Gnomad4 AMR AF: 0.00517

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00432

Gnomad4 OTH AF: 0.00856

Alfa AF: 0.00145 Hom.: 0

Bravo AF: 0.0104

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.41
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41265282; hg19: chr9-13115349;