Genetic Variant MPP1:p.Arg389Gln (chrX-154781297-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_002436.4(MPP1):c.1166G>A(p.Arg389Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0001 in 1,198,078 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 38 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., 7 hem., cov: 21)

Exomes 𝑓: 0.000079 ( 0 hom. 31 hem. )

Consequence

MPP1
NM_002436.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.05

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.29358175).

BS2

High Hemizygotes in GnomAd4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002436.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPP1	NM_002436.4	MANE Select	c.1166G>A	p.Arg389Gln	missense	Exon 11 of 12	NP_002427.1	Q00013-1
MPP1	NM_001166460.2		c.1115G>A	p.Arg372Gln	missense	Exon 11 of 12	NP_001159932.1
MPP1	NM_001166461.2		c.1106G>A	p.Arg369Gln	missense	Exon 11 of 12	NP_001159933.1	Q00013-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPP1	ENST00000369534.8	TSL:1 MANE Select	c.1166G>A	p.Arg389Gln	missense	Exon 11 of 12	ENSP00000358547.3	Q00013-1
MPP1	ENST00000393531.5	TSL:1	c.1106G>A	p.Arg369Gln	missense	Exon 11 of 12	ENSP00000377165.1	Q00013-3
MPP1	ENST00000934478.1		c.1166G>A	p.Arg389Gln	missense	Exon 12 of 13	ENSP00000604537.1

Frequencies

GnomAD3 genomes

AF:

0.000330

AC:

AN:

102915

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

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:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000991

AC:

AN:

181697

AF XY:

0.000136

show subpopulations

Gnomad AFR exome

AF:

0.000762

Gnomad AMR exome

AF:

0.0000736

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000492

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000785

AC:

AN:

1095163

Hom.:

Cov.:

AF XY:

0.0000860

AC XY:

AN XY:

360603

show subpopulations

African (AFR)

AF:

0.00171

AC:

AN:

26292

American (AMR)

AF:

0.0000856

AC:

AN:

35058

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19348

East Asian (EAS)

AF:

0.00

AC:

AN:

30178

South Asian (SAS)

AF:

0.0000372

AC:

AN:

53775

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40507

Middle Eastern (MID)

AF:

0.00123

AC:

AN:

4077

European-Non Finnish (NFE)

AF:

0.0000310

AC:

AN:

839956

Other (OTH)

AF:

0.000109

AC:

AN:

45972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000330

AC:

AN:

102915

Hom.:

Cov.:

AF XY:

0.000263

AC XY:

AN XY:

26655

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

27527

American (AMR)

AF:

0.00

AC:

AN:

9301

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2573

East Asian (EAS)

AF:

0.00

AC:

AN:

3333

South Asian (SAS)

AF:

0.00

AC:

AN:

2186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4803

Middle Eastern (MID)

AF:

0.00

AC:

AN:

224

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

50966

Other (OTH)

AF:

0.00

AC:

AN:

1340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000432

Hom.:

Bravo

AF:

0.000412

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.28

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.48

MutationAssessor

Pathogenic

3.0

PhyloP100

6.0

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.47

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.23

MVP

0.82

MPC

0.67

ClinPred

0.23

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.95

gMVP

0.88

Mutation Taster

=73/27

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over