X-154792236-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002436.4(MPP1):c.152G>A(p.Gly51Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000504 in 1,210,343 control chromosomes in the GnomAD database, including 1 homozygotes. There are 23 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G51G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000051 ( 1 hom. 21 hem. )

Consequence

MPP1
NM_002436.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.86

Variant links:

Genes affected

MPP1 (HGNC:7219): (MAGUK p55 scaffold protein 1) This gene encodes the prototype of the membrane-associated guanylate kinase (MAGUK) family proteins. MAGUKs interact with the cytoskeleton and regulate cell proliferation, signaling pathways, and intercellular junctions. The encoded protein is an extensively palmitoylated membrane phosphoprotein containing a PDZ domain, a Src homology 3 (SH3) motif, and a guanylate kinase domain. This gene product interacts with various cytoskeletal proteins and cell junctional proteins in different tissue and cell types, and may be involved in the regulation of cell shape, hair cell development, neural patterning of the retina, and apico-basal polarity and tumor suppression pathways in non-erythroid cells. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

MPP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019574374).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP1	NM_002436.4 link	c.152G>A	p.Gly51Glu	missense_variant	Exon 2 of 12	ENST00000369534.8	NP_002427.1	Q00013-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP1	ENST00000369534.8 link	c.152G>A	p.Gly51Glu	missense_variant	Exon 2 of 12	1	NM_002436.4	ENSP00000358547.3		Q00013-1

Frequencies

GnomAD3 genomes

AF:

0.0000534

AC:

AN:

112279

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

34429

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000187

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00148

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000153

AC:

AN:

182675

Hom.:

AF XY:

0.000148

AC XY:

AN XY:

67343

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000840

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.0000510

AC:

AN:

1098011

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

363377

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000312

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000739

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.0000445

AC:

AN:

112332

Hom.:

Cov.:

AF XY:

0.0000580

AC XY:

AN XY:

34492

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000187

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00111

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000425

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.152G>A (p.G51E) alteration is located in exon 2 (coding exon 2) of the MPP1 gene. This alteration results from a G to A substitution at nucleotide position 152, causing the glycine (G) at amino acid position 51 to be replaced by a glutamic acid (E). 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

0.31

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.64

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.26

T;.;.;.;.

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.80

T;T;T;T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.020

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;.;L;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.3

N;N;N;D;N

REVEL

Benign

0.15

Sift

Benign

0.048

D;T;D;D;D

Sift4G

Benign

0.12

T;T;T;.;.

Polyphen

1.0

D;.;.;.;.

Vest4

0.069

MutPred

0.17

Loss of relative solvent accessibility (P = 0.0676);.;Loss of relative solvent accessibility (P = 0.0676);.;Loss of relative solvent accessibility (P = 0.0676);

MVP

0.59

MPC

1.6

ClinPred

0.043

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.18

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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