chr1-156909831-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001080471.3(PEAR1):c.1492C>T(p.His498Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
PEAR1
NM_001080471.3 missense
NM_001080471.3 missense
Scores
7
11
Clinical Significance
Conservation
PhyloP100: 1.15
Genes affected
PEAR1 (HGNC:33631): (platelet endothelial aggregation receptor 1) PEAR1 is a platelet receptor that signals upon the formation of platelet-platelet contacts independent of platelet activation and secondary to platelet aggregation (Nanda et al., 2005 [PubMed 15851471]).[supplied by OMIM, Mar 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=0.13267273).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PEAR1 | NM_001080471.3 | c.1492C>T | p.His498Tyr | missense_variant | 12/23 | ENST00000292357.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PEAR1 | ENST00000292357.8 | c.1492C>T | p.His498Tyr | missense_variant | 12/23 | 5 | NM_001080471.3 | P1 | |
PEAR1 | ENST00000338302.7 | c.1492C>T | p.His498Tyr | missense_variant | 13/24 | 5 | P1 | ||
PEAR1 | ENST00000469390.5 | n.1220C>T | non_coding_transcript_exon_variant | 7/18 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152234Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251162Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135776
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461670Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727124
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152350Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74502
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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 | Dec 21, 2022 | The c.1492C>T (p.H498Y) alteration is located in exon 12 (coding exon 11) of the PEAR1 gene. This alteration results from a C to T substitution at nucleotide position 1492, causing the histidine (H) at amino acid position 498 to be replaced by a tyrosine (Y). 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;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;P
Vest4
MutPred
Loss of disorder (P = 0.0375);Loss of disorder (P = 0.0375);
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