18-7774215-A-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001105244.2(PTPRM):āc.140A>Gā(p.Asn47Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,613,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000033 ( 0 hom., cov: 33)
Exomes š: 0.000015 ( 0 hom. )
Consequence
PTPRM
NM_001105244.2 missense
NM_001105244.2 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 5.42
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.
BP4
Computational evidence support a benign effect (MetaRNN=0.39069796).
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTPRM | NM_001105244.2 | c.140A>G | p.Asn47Ser | missense_variant | 2/33 | ENST00000580170.6 | NP_001098714.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTPRM | ENST00000580170.6 | c.140A>G | p.Asn47Ser | missense_variant | 2/33 | 1 | NM_001105244.2 | ENSP00000463325 | A1 | |
PTPRM | ENST00000332175.12 | c.140A>G | p.Asn47Ser | missense_variant | 2/31 | 1 | ENSP00000331418 | P4 | ||
PTPRM | ENST00000400053.8 | c.-47A>G | 5_prime_UTR_variant | 2/31 | 5 | ENSP00000382927 | ||||
PTPRM | ENST00000400060.8 | c.-3419A>G | 5_prime_UTR_variant | 1/32 | 5 | ENSP00000382933 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152188Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251452Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135900
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461560Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 727120
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74358
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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 17, 2022 | The c.140A>G (p.N47S) alteration is located in exon 2 (coding exon 2) of the PTPRM gene. This alteration results from a A to G substitution at nucleotide position 140, causing the asparagine (N) at amino acid position 47 to be replaced by a serine (S). 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
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
.;N
REVEL
Benign
Sift
Benign
.;D
Sift4G
Uncertain
D;D
Polyphen
0.83
.;P
Vest4
MutPred
Gain of disorder (P = 0.0565);Gain of disorder (P = 0.0565);
MVP
MPC
ClinPred
T
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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