rs10756457

Positions:

• chr9-13150532-T-A
• chr9-13150532-T-C
• chr9-13150532-T-G

Variant summary

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

The NM_001378778.1(MPDZ):​c.3609A>T​(p.Lys1203Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K1203K) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MPDZ NM_001378778.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPDZ	NM_001378778.1	c.3609A>T	p.Lys1203Asn	missense_variant	25/47	ENST00000319217.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPDZ	ENST00000319217.12	c.3609A>T	p.Lys1203Asn	missense_variant	25/47	5	NM_001378778.1	A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1419172 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 704960

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;.;.;.;.;.;.;.;.;T
Eigen	Benign	0.012
Eigen_PC	Benign	-0.052
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;.;D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.67	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	M;M;M;.;.;M;M;.;.;.
MutationTaster	Benign	0.099	P;P;P;P;P;P;P;P
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-4.6	D;D;D;D;D;D;D;D;D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0090	D;D;D;D;D;D;D;D;D;T
Sift4G	Uncertain	0.0030	D;D;D;D;D;D;D;D;.;.
Polyphen		0.96, 0.87	.;D;D;.;P;.;D;.;.;.
Vest4		0.65
MutPred		0.61		.;.;.;.;Loss of ubiquitination at K95 (P = 0.0192);.;.;.;Loss of ubiquitination at K95 (P = 0.0192);Loss of ubiquitination at K95 (P = 0.0192);
MVP		0.32
ClinPred		0.98	D
GERP RS		0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10756457; hg19: chr9-13150531;