chr9-13189018-T-C

Position:

• chr9-13189018-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001378778.1(MPDZ):​c.2155-25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,593,518 control chromosomes in the GnomAD database, including 244 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.013 (27 hom., cov: 32)
  • Exomes 𝑓: 0.015 (217 hom.)
• Consequence: MPDZ NM_001378778.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0127 (1925/152138) while in subpopulation AMR AF= 0.0173 (264/15264). AF 95% confidence interval is 0.0163. There are 27 homozygotes in gnomad4. There are 927 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.2155-25A>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.2155-25A>G		intron_variant		5	NM_001378778.1	ENSP00000320006.7

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1927 AN: 152020 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.00341

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.0136

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0182

GnomAD3 exomes AF: 0.0137 AC: 3257 AN: 237858 Hom.: 47 AF XY: 0.0140 AC XY: 1814 AN XY: 129126

Gnomad AFR exome AF: 0.00239

Gnomad AMR exome AF: 0.0114

Gnomad ASJ exome AF: 0.0441

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00461

Gnomad FIN exome AF: 0.0147

Gnomad NFE exome AF: 0.0175

Gnomad OTH exome AF: 0.0184

GnomAD4 exome AF: 0.0154 AC: 22197 AN: 1441380 Hom.: 217 Cov.: 27 AF XY: 0.0154 AC XY: 11046 AN XY: 715788

Gnomad4 AFR exome AF: 0.00310

Gnomad4 AMR exome AF: 0.0122

Gnomad4 ASJ exome AF: 0.0439

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00450

Gnomad4 FIN exome AF: 0.0125

Gnomad4 NFE exome AF: 0.0166

Gnomad4 OTH exome AF: 0.0174

GnomAD4 genome AF: 0.0127 AC: 1925 AN: 152138 Hom.: 27 Cov.: 32 AF XY: 0.0125 AC XY: 927 AN XY: 74348

Gnomad4 AFR AF: 0.00340

Gnomad4 AMR AF: 0.0173

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.0136

Gnomad4 NFE AF: 0.0171

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0169 Hom.: 8

Bravo AF: 0.0129

Asia WGS AF: 0.00260 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Benign	0.71
La Branchor		0.84
BranchPoint Hunter		6.0

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: rs41265290; hg19: chr9-13189017;