17-43814241-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001932.6(MPP3):āc.1130A>Gā(p.Tyr377Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000465 in 1,613,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.000049 ( 0 hom. )
Consequence
MPP3
NM_001932.6 missense
NM_001932.6 missense
Scores
6
9
4
Clinical Significance
Conservation
PhyloP100: 6.93
Genes affected
MPP3 (HGNC:7221): (MAGUK p55 scaffold protein 3) This gene product is a member of a family of membrane-associated proteins termed MAGUKs (membrane-associated guanylate kinase homologs). MAGUKs interact with the cytoskeleton and regulate cell proliferation, signaling pathways, and intracellular junctions. This protein contains a conserved sequence, called the SH3 (src homology 3) motif, found in several other proteins that associate with the cytoskeleton and are suspected to play important roles in signal transduction. Alternatively spliced transcript variants have been identified. One transcript variant is experimentally supported, but it doesn't encode a protein. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.802
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MPP3 | NM_001932.6 | c.1130A>G | p.Tyr377Cys | missense_variant | 15/20 | ENST00000398389.9 | NP_001923.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MPP3 | ENST00000398389.9 | c.1130A>G | p.Tyr377Cys | missense_variant | 15/20 | 1 | NM_001932.6 | ENSP00000381425 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000803 AC: 2AN: 248974Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135130
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GnomAD4 exome AF: 0.0000493 AC: 72AN: 1461392Hom.: 0 Cov.: 32 AF XY: 0.0000495 AC XY: 36AN XY: 727018
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74342
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 17, 2023 | The c.1130A>G (p.Y377C) alteration is located in exon 15 (coding exon 13) of the MPP3 gene. This alteration results from a A to G substitution at nucleotide position 1130, causing the tyrosine (Y) at amino acid position 377 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;D
Vest4
MutPred
Loss of phosphorylation at Y402 (P = 0.0277);.;
MVP
MPC
1.4
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at