X-154785146-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002436.4(MPP1):​c.689G>A​(p.Ser230Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Consequence

MPP1
NM_002436.4 missense

Scores

2
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33340037).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MPP1NM_002436.4 linkc.689G>A p.Ser230Asn missense_variant Exon 7 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.689G>A p.Ser230Asn missense_variant Exon 7 of 12 1 NM_002436.4 ENSP00000358547.3 Q00013-1

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
22

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.689G>A (p.S230N) alteration is located in exon 7 (coding exon 7) of the MPP1 gene. This alteration results from a G to A substitution at nucleotide position 689, causing the serine (S) at amino acid position 230 to be replaced by an asparagine (N). 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
0.23
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
17
DANN
Benign
0.96
DEOGEN2
Benign
0.22
T;.;.;.;.;.
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;D;D;D;D;D
M_CAP
Pathogenic
0.71
D
MetaRNN
Benign
0.33
T;T;T;T;T;T
MetaSVM
Uncertain
0.20
D
MutationAssessor
Benign
1.6
L;.;.;.;.;.
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-1.8
N;N;N;N;N;N
REVEL
Uncertain
0.34
Sift
Benign
0.31
T;T;T;T;T;T
Sift4G
Benign
0.30
T;T;T;.;.;.
Polyphen
0.10
B;.;.;D;.;.
Vest4
0.48
MutPred
0.22
Loss of phosphorylation at S230 (P = 0.0168);.;.;.;.;.;
MVP
0.85
MPC
1.1
ClinPred
0.73
D
GERP RS
5.6
Varity_R
0.46
gMVP
0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-154013421; COSMIC: COSV65728017; COSMIC: COSV65728017; API