3-62003354-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002841.4(PTPRG):āc.376A>Gā(p.Ile126Val) variant causes a missense change. The variant allele was found at a frequency of 0.000191 in 1,613,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00017 ( 0 hom., cov: 33)
Exomes š: 0.00019 ( 0 hom. )
Consequence
PTPRG
NM_002841.4 missense
NM_002841.4 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 4.79
Genes affected
PTPRG (HGNC:9671): (protein tyrosine phosphatase receptor type G) 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 intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region of this PTP contains a carbonic anhydrase-like (CAH) domain, which is also found in the extracellular region of PTPRBETA/ZETA. This gene is located in a chromosomal region that is frequently deleted in renal cell carcinoma and lung carcinoma, thus is thought to be a candidate tumor suppressor gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09555724).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTPRG | NM_002841.4 | c.376A>G | p.Ile126Val | missense_variant | 4/30 | ENST00000474889.6 | NP_002832.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTPRG | ENST00000474889.6 | c.376A>G | p.Ile126Val | missense_variant | 4/30 | 1 | NM_002841.4 | ENSP00000418112 | A1 | |
PTPRG | ENST00000295874.14 | c.376A>G | p.Ile126Val | missense_variant | 4/29 | 1 | ENSP00000295874 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152190Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000136 AC: 34AN: 250562Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135412
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GnomAD4 exome AF: 0.000193 AC: 282AN: 1461326Hom.: 0 Cov.: 30 AF XY: 0.000190 AC XY: 138AN XY: 726958
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GnomAD4 genome AF: 0.000171 AC: 26AN: 152308Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74490
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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 | Oct 21, 2021 | The c.376A>G (p.I126V) alteration is located in exon 4 (coding exon 4) of the PTPRG gene. This alteration results from a A to G substitution at nucleotide position 376, causing the isoleucine (I) at amino acid position 126 to be replaced by a valine (V). 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
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
0.17
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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