9-13105639-T-C

Variant names:

• chr9-13105639-T-C
• rs10733253
• NM_001378778.1:c.*1326A>G

Variant summary

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

The NM_001378778.1(MPDZ):​c.*1326A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,174 control chromosomes in the GnomAD database, including 56,364 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 0.85 (56364 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MPDZ NM_001378778.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

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=-0.59).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.*1326A>G		downstream_gene_variant		ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.*1326A>G		downstream_gene_variant		5	NM_001378778.1	ENSP00000320006.7
MPDZ	ENST00000541718.5	c.*1326A>G		downstream_gene_variant		1		ENSP00000439807.1
MPDZ	ENST00000381017.6	n.*67A>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129860 AN: 152056 Hom.: 56358 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.949

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.942

Gnomad OTH AF: 0.880

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.854 AC: 129910 AN: 152174 Hom.: 56364 Cov.: 32 AF XY: 0.855 AC XY: 63629 AN XY: 74408

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.824

Gnomad4 ASJ AF: 0.918

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.949

Gnomad4 NFE AF: 0.942

Gnomad4 OTH AF: 0.875

Alfa AF: 0.878 Hom.: 5062

Bravo AF: 0.839

Asia WGS AF: 0.797 AC: 2770 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10733253; hg19: chr9-13105638;