Genetic Variant MPP1:p.Gly51Gly (chrX-154792235-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002436.4(MPP1):c.153G>A(p.Gly51Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00044 in 1,210,436 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 164 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., 10 hem., cov: 23)

Exomes 𝑓: 0.00044 ( 0 hom. 154 hem. )

Consequence

MPP1
NM_002436.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.75

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-154792235-C-T is Benign according to our data. Variant chrX-154792235-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 709326.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.75 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP1	NM_002436.4 link	c.153G>A	p.Gly51Gly	synonymous_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.153G>A	p.Gly51Gly	synonymous_variant	Exon 2 of 12	1	NM_002436.4	ENSP00000358547.3		Q00013-1

Frequencies

GnomAD3 genomes

AF:

0.000400

AC:

AN:

112380

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

AN XY:

34536

show subpopulations

Gnomad AFR

AF:

0.0000972

Gnomad AMI

AF:

0.00583

Gnomad AMR

AF:

0.000281

Gnomad ASJ

AF:

0.00264

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000367

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000507

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000422

AC:

AN:

182653

Hom.:

AF XY:

0.000535

AC XY:

AN XY:

67335

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000548

Gnomad ASJ exome

AF:

0.00201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000525

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000529

Gnomad OTH exome

AF:

0.000664

GnomAD4 exome

AF:

0.000444

AC:

488

AN:

1098004

Hom.:

Cov.:

AF XY:

0.000424

AC XY:

154

AN XY:

363370

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.000426

Gnomad4 ASJ exome

AF:

0.00170

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000111

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000476

Gnomad4 OTH exome

AF:

0.000586

GnomAD4 genome

AF:

0.000400

AC:

AN:

112432

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

AN XY:

34598

show subpopulations

Gnomad4 AFR

AF:

0.0000970

Gnomad4 AMR

AF:

0.000281

Gnomad4 ASJ

AF:

0.00264

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000368

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000507

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000654

Hom.:

Bravo

AF:

0.000412

EpiCase

AF:

0.000984

EpiControl

AF:

0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.7

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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