18-7955281-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_001105244.2(PTPRM):c.999C>T(p.Val333=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,614,062 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.012 ( 46 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 32 hom. )
Consequence
PTPRM
NM_001105244.2 synonymous
NM_001105244.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.606
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 Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
?
Variant 18-7955281-C-T is Benign according to our data. Variant chr18-7955281-C-T is described in ClinVar as [Benign]. Clinvar id is 713214.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.606 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1809/152198) while in subpopulation AFR AF= 0.0416 (1726/41530). AF 95% confidence interval is 0.0399. There are 46 homozygotes in gnomad4. There are 865 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1800 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPRM | NM_001105244.2 | c.999C>T | p.Val333= | synonymous_variant | 7/33 | ENST00000580170.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPRM | ENST00000580170.6 | c.999C>T | p.Val333= | synonymous_variant | 7/33 | 1 | NM_001105244.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0118 AC: 1800AN: 152080Hom.: 46 Cov.: 32
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GnomAD3 exomes AF: 0.00324 AC: 813AN: 251256Hom.: 10 AF XY: 0.00227 AC XY: 308AN XY: 135818
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GnomAD4 exome AF: 0.00125 AC: 1828AN: 1461864Hom.: 32 Cov.: 31 AF XY: 0.00108 AC XY: 788AN XY: 727230
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 16, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at