chr20-42098534-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_007050.6(PTPRT):c.3733G>A(p.Ala1245Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000238 in 1,613,976 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00023 ( 1 hom. )
Consequence
PTPRT
NM_007050.6 missense
NM_007050.6 missense
Scores
4
12
3
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
PTPRT (HGNC:9682): (protein tyrosine phosphatase receptor type T) 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 intracellular catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains a meprin-A5 antigen-PTP (MAM) domain, Ig-like and fibronectin type III-like repeats. The protein domain structure and the expression pattern of the mouse counterpart of this PTP suggest its roles in both signal transduction and cellular adhesion in the central nervous system. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP2
Missense variant where missense usually causes diseases, PTPRT
BS2
High AC in GnomAd4 at 41 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPRT | NM_007050.6 | c.3733G>A | p.Ala1245Thr | missense_variant | 27/31 | ENST00000373187.6 | |
LOC101927182 | XR_001754611.2 | n.567+7597C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPRT | ENST00000373187.6 | c.3733G>A | p.Ala1245Thr | missense_variant | 27/31 | 1 | NM_007050.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000269 AC: 41AN: 152148Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000173 AC: 43AN: 249148Hom.: 0 AF XY: 0.000185 AC XY: 25AN XY: 135162
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GnomAD4 exome AF: 0.000235 AC: 343AN: 1461828Hom.: 1 Cov.: 31 AF XY: 0.000232 AC XY: 169AN XY: 727210
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GnomAD4 genome AF: 0.000269 AC: 41AN: 152148Hom.: 0 Cov.: 33 AF XY: 0.000229 AC XY: 17AN XY: 74334
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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 | Mar 28, 2024 | The c.3790G>A (p.A1264T) alteration is located in exon 28 (coding exon 28) of the PTPRT gene. This alteration results from a G to A substitution at nucleotide position 3790, causing the alanine (A) at amino acid position 1264 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
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;D;D;D;.;D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;.;D;.;.
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D;.;D;.;.
Sift4G
Uncertain
T;T;T;T;T;T;T;T
Polyphen
D;.;.;.;.;.;.;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
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