9-13140097-G-C

Position:

• chr9-13140097-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378778.1(MPDZ):​c.3893C>G​(p.Pro1298Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPDZ NM_001378778.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25173467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.3893C>G	p.Pro1298Arg	missense_variant	28/47	ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.3893C>G	p.Pro1298Arg	missense_variant	28/47	5	NM_001378778.1	ENSP00000320006.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.14	T;.;.;.;.;.;.;.;.
Eigen	Benign	-0.0035
Eigen_PC	Benign	-0.018
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D;.;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L;.;.;.;.;.;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-4.4	D;D;.;D;D;D;D;D;D
REVEL	Benign	0.040
Sift	Uncertain	0.0080	D;D;.;T;T;T;T;D;T
Sift4G	Uncertain	0.038	D;D;T;T;T;T;T;D;.
Polyphen		0.91, 0.81, 0.55	.;P;P;.;P;.;P;.;.
Vest4		0.46
MutPred		0.34		.;.;.;.;Loss of glycosylation at P157 (P = 0.0125);.;.;.;.;
MVP		0.38
ClinPred		0.66	D
GERP RS		3.0
Varity_R		0.096
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-13140096;