9-13123296-T-G

Variant names:

• chr9-13123296-T-G
• rs16930134
• NM_001378778.1:c.4810A>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.4810A>C​(p.Thr1604Pro) variant causes a missense, splice region 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. 13/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1604A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPDZ NM_001378778.1 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487

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 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=0.14078626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDZ	NM_001378778.1	c.4810A>C	p.Thr1604Pro	missense_variant, splice_region_variant	Exon 36 of 47	ENST00000319217.12	NP_001365707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPDZ	ENST00000319217.12	c.4810A>C	p.Thr1604Pro	missense_variant, splice_region_variant	Exon 36 of 47	5	NM_001378778.1	ENSP00000320006.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.041	T;.;.;.;.;.;.;.;.
Eigen	Benign	-0.079
Eigen_PC	Benign	-0.059
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.85	T;T;T;D;T;T;T;.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M;.;.;.;.;.;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.9	N;N;.;N;N;N;N;N;N
REVEL	Benign	0.034
Sift	Benign	0.046	D;T;.;T;D;T;T;T;D
Sift4G	Benign	0.27	T;T;T;T;T;T;T;T;T
Polyphen		0.11	B;P;P;.;.;B;.;P;.
Vest4		0.14
MutPred		0.25		Loss of phosphorylation at T1604 (P = 0.0097);Loss of phosphorylation at T1604 (P = 0.0097);.;.;.;.;.;.;.;
MVP		0.36
ClinPred		0.90	D
GERP RS		0.48
Varity_R		0.62
gMVP		0.34

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: rs16930134; hg19: chr9-13123295;