18-7955153-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001105244.2(PTPRM):c.871G>A(p.Ala291Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00015 in 1,611,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 0 hom. )
Consequence
PTPRM
NM_001105244.2 missense
NM_001105244.2 missense
Scores
3
12
Clinical Significance
Conservation
PhyloP100: 4.26
Genes affected
PTPRM (HGNC:9675): (protein tyrosine phosphatase receptor type M) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and two tandem catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP mu (MAM) domain, an Ig-like domain and four fibronectin type III-like repeats. This PTP has been shown to mediate cell-cell aggregation through the interaction with another molecule of this PTP on an adjacent cell. This PTP can interact with scaffolding protein RACK1/GNB2L1, which may be necessary for the downstream signaling in response to cell-cell adhesion. Alternative splicing results in multiple transcripts encoding distinct isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
Missense variant where missense usually causes diseases, PTPRM
BP4
Computational evidence support a benign effect (MetaRNN=0.07025361).
BS2
High AC in GnomAd4 at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPRM | NM_001105244.2 | c.871G>A | p.Ala291Thr | missense_variant | 7/33 | ENST00000580170.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPRM | ENST00000580170.6 | c.871G>A | p.Ala291Thr | missense_variant | 7/33 | 1 | NM_001105244.2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152142Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000839 AC: 21AN: 250386Hom.: 0 AF XY: 0.0000887 AC XY: 12AN XY: 135262
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GnomAD4 exome AF: 0.000154 AC: 225AN: 1458930Hom.: 0 Cov.: 31 AF XY: 0.000146 AC XY: 106AN XY: 725098
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GnomAD4 genome AF: 0.000105 AC: 16AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74322
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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 | Aug 13, 2021 | The c.871G>A (p.A291T) alteration is located in exon 7 (coding exon 7) of the PTPRM gene. This alteration results from a G to A substitution at nucleotide position 871, causing the alanine (A) at amino acid position 291 to be replaced by a threonine (T). 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
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T;T
Polyphen
0.0010
.;B;.;.
Vest4
MVP
MPC
ClinPred
T
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