Variant 17-43818067-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001932.6(MPP3):c.925C>A(p.Gln309Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00005 in 1,580,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

MPP3
NM_001932.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.92

Variant links:

Genes affected

MPP3 (HGNC:7221): (MAGUK p55 scaffold protein 3) This gene product is a member of a family of membrane-associated proteins termed MAGUKs (membrane-associated guanylate kinase homologs). MAGUKs interact with the cytoskeleton and regulate cell proliferation, signaling pathways, and intracellular junctions. This protein contains a conserved sequence, called the SH3 (src homology 3) motif, found in several other proteins that associate with the cytoskeleton and are suspected to play important roles in signal transduction. Alternatively spliced transcript variants have been identified. One transcript variant is experimentally supported, but it doesn't encode a protein. [provided by RefSeq, Jul 2008]

MPP3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011411607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPP3	NM_001932.6 linkuse as main transcript	c.925C>A	p.Gln309Lys	missense_variant	12/20	ENST00000398389.9	NP_001923.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPP3	ENST00000398389.9 linkuse as main transcript	c.925C>A	p.Gln309Lys	missense_variant	12/20	1	NM_001932.6	ENSP00000381425	P1	Q13368-1

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000524

AC:

AN:

209832

Hom.:

AF XY:

0.0000174

AC XY:

AN XY:

114834

show subpopulations

Gnomad AFR exome

AF:

0.000767

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000105

Gnomad OTH exome

AF:

0.000202

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1428166

Hom.:

Cov.:

AF XY:

0.0000240

AC XY:

AN XY:

708482

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.0000242

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:

9.14e-7

Gnomad4 OTH exome

AF:

0.0000848

GnomAD4 genome

AF:

0.000223

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000103

Hom.:

Bravo

AF:

0.000246

ESP6500AA

AF:

0.000819

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2023

The c.925C>A (p.Q309K) alteration is located in exon 12 (coding exon 10) of the MPP3 gene. This alteration results from a C to A substitution at nucleotide position 925, causing the glutamine (Q) at amino acid position 309 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.019

.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

.;L

MutationTaster

Benign

0.77

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.056

Sift

Benign

0.71

T;T

Sift4G

Benign

0.81

T;T

Polyphen

0.0

B;B

Vest4

0.23

MVP

0.39

MPC

0.56

ClinPred

0.028

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.090

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over