chr20-3027761-A-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001385305.1(PTPRA):āc.1840A>Gā(p.Ile614Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000731 in 1,614,066 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000046 ( 0 hom., cov: 32)
Exomes š: 0.000076 ( 3 hom. )
Consequence
PTPRA
NM_001385305.1 missense
NM_001385305.1 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 3.64
Genes affected
PTPRA (HGNC:9664): (protein tyrosine phosphatase receptor type A) 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 contains an extracellular domain, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. This PTP has been shown to dephosphorylate and activate Src family tyrosine kinases, and is implicated in the regulation of integrin signaling, cell adhesion and proliferation. Three alternatively spliced variants of this gene, which encode two distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPRA | NM_001385305.1 | c.1840A>G | p.Ile614Val | missense_variant | 20/24 | ENST00000399903.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPRA | ENST00000399903.7 | c.1840A>G | p.Ile614Val | missense_variant | 20/24 | 5 | NM_001385305.1 | P4 | |
PTPRA | ENST00000216877.10 | c.1813A>G | p.Ile605Val | missense_variant | 19/23 | 1 | A1 | ||
PTPRA | ENST00000356147.3 | c.1813A>G | p.Ile605Val | missense_variant | 19/23 | 1 | A1 | ||
PTPRA | ENST00000318266.9 | c.1813A>G | p.Ile605Val | missense_variant | 20/24 | 5 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152090Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000171 AC: 43AN: 251412Hom.: 2 AF XY: 0.000243 AC XY: 33AN XY: 135878
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GnomAD4 exome AF: 0.0000759 AC: 111AN: 1461858Hom.: 3 Cov.: 31 AF XY: 0.0000990 AC XY: 72AN XY: 727226
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74414
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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 | Jan 22, 2024 | The c.1840A>G (p.I614V) alteration is located in exon 24 (coding exon 17) of the PTPRA gene. This alteration results from a A to G substitution at nucleotide position 1840, causing the isoleucine (I) at amino acid position 614 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
Uncertain
DANN
Benign
DEOGEN2
Benign
T;.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
B;.;B;.;.
Vest4
MVP
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at