18-7774215-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001105244.2(PTPRM):ā€‹c.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

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.42
Variant links:
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]

Genome browser will be placed here

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
PTPRMNM_001105244.2 linkuse as main transcriptc.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
PTPRMENST00000580170.6 linkuse as main transcriptc.140A>G p.Asn47Ser missense_variant 2/331 NM_001105244.2 ENSP00000463325 A1P28827-2
PTPRMENST00000332175.12 linkuse as main transcriptc.140A>G p.Asn47Ser missense_variant 2/311 ENSP00000331418 P4P28827-1
PTPRMENST00000400053.8 linkuse as main transcriptc.-47A>G 5_prime_UTR_variant 2/315 ENSP00000382927
PTPRMENST00000400060.8 linkuse as main transcriptc.-3419A>G 5_prime_UTR_variant 1/325 ENSP00000382933

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152188
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251452
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000867
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000151
AC:
22
AN:
1461560
Hom.:
0
Cov.:
32
AF XY:
0.0000206
AC XY:
15
AN XY:
727120
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000810
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152188
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000675
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsAug 17, 2022The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.051
.;T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.39
T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
0.90
L;L
MutationTaster
Benign
0.67
D;D;D;D
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.32
.;N
REVEL
Benign
0.16
Sift
Benign
0.032
.;D
Sift4G
Uncertain
0.025
D;D
Polyphen
0.83
.;P
Vest4
0.33
MutPred
0.49
Gain of disorder (P = 0.0565);Gain of disorder (P = 0.0565);
MVP
0.61
MPC
0.46
ClinPred
0.35
T
GERP RS
5.6
Varity_R
0.33
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs776571679; hg19: chr18-7774213; API