rs13291548

Positions:

• chr9-13192049-T-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.1968+82A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,239,456 control chromosomes in the GnomAD database, including 158 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 0.012 (15 hom., cov: 32)
  • Exomes 𝑓: 0.014 (143 hom.)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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 nfe. gnomad4 allele frequency = 0.0117 (1786/152220) while in subpopulation NFE AF= 0.0182 (1238/67984). AF 95% confidence interval is 0.0174. There are 15 homozygotes in gnomad4. There are 870 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.1968+82A>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.1968+82A>G		intron_variant		5	NM_001378778.1	ENSP00000320006	A1

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1785 AN: 152102 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00849

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0182

Gnomad OTH AF: 0.0182

GnomAD4 exome AF: 0.0142 AC: 15392 AN: 1087236 Hom.: 143 AF XY: 0.0140 AC XY: 7390 AN XY: 526410

Gnomad4 AFR exome AF: 0.00216

Gnomad4 AMR exome AF: 0.0123

Gnomad4 ASJ exome AF: 0.0161

Gnomad4 EAS exome AF: 0.0000320

Gnomad4 SAS exome AF: 0.00253

Gnomad4 FIN exome AF: 0.00910

Gnomad4 NFE exome AF: 0.0155

Gnomad4 OTH exome AF: 0.0161

GnomAD4 genome AF: 0.0117 AC: 1786 AN: 152220 Hom.: 15 Cov.: 32 AF XY: 0.0117 AC XY: 870 AN XY: 74418

Gnomad4 AFR AF: 0.00253

Gnomad4 AMR AF: 0.0156

Gnomad4 ASJ AF: 0.0144

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.00849

Gnomad4 NFE AF: 0.0182

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0136 Hom.: 2

Bravo AF: 0.0113

Asia WGS AF: 0.00375 AC: 14 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	0.70
DANN	Benign	0.84

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: rs13291548; hg19: chr9-13192048;