X-154792207-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002436.4(MPP1):​c.181G>T​(p.Val61Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 1,210,227 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 102 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., 52 hem., cov: 23)
Exomes 𝑓: 0.00017 ( 0 hom. 50 hem. )

Consequence

MPP1
NM_002436.4 missense

Scores

1
16

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0970
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.002958268).
BP6
Variant X-154792207-C-A is Benign according to our data. Variant chrX-154792207-C-A is described in ClinVar as [Benign]. Clinvar id is 727529.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 52 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MPP1NM_002436.4 linkc.181G>T p.Val61Phe 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
MPP1ENST00000369534.8 linkc.181G>T p.Val61Phe missense_variant Exon 2 of 12 1 NM_002436.4 ENSP00000358547.3 Q00013-1

Frequencies

GnomAD3 genomes
AF:
0.00164
AC:
184
AN:
112212
Hom.:
0
Cov.:
23
AF XY:
0.00154
AC XY:
53
AN XY:
34362
show subpopulations
Gnomad AFR
AF:
0.00569
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000469
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:
0.00
Gnomad OTH
AF:
0.00265
GnomAD3 exomes
AF:
0.000405
AC:
74
AN:
182848
Hom.:
0
AF XY:
0.000252
AC XY:
17
AN XY:
67476
show subpopulations
Gnomad AFR exome
AF:
0.00533
Gnomad AMR exome
AF:
0.000146
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000168
AC:
185
AN:
1097961
Hom.:
0
Cov.:
30
AF XY:
0.000138
AC XY:
50
AN XY:
363327
show subpopulations
Gnomad4 AFR exome
AF:
0.00633
Gnomad4 AMR exome
AF:
0.000170
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000185
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000239
GnomAD4 genome
AF:
0.00163
AC:
183
AN:
112266
Hom.:
0
Cov.:
23
AF XY:
0.00151
AC XY:
52
AN XY:
34426
show subpopulations
Gnomad4 AFR
AF:
0.00564
Gnomad4 AMR
AF:
0.000469
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00262
Alfa
AF:
0.000199
Hom.:
6
Bravo
AF:
0.00189
ESP6500AA
AF:
0.00443
AC:
17
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000412
AC:
50

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Dec 14, 2017
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
13
DANN
Benign
0.13
DEOGEN2
Benign
0.15
T;.;.;.;.
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.83
T;T;T;T;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.0030
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L;.;L;.;.
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.4
N;N;N;N;N
REVEL
Benign
0.0070
Sift
Benign
0.98
T;T;T;T;T
Sift4G
Benign
0.80
T;T;T;.;.
Polyphen
0.0010
B;.;.;.;.
Vest4
0.18
MVP
0.22
MPC
0.65
ClinPred
0.0064
T
GERP RS
2.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.18
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs143824239; hg19: chrX-154020482; API