16-88733731-C-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001142864.4(PIEZO1):c.2344G>A(p.Gly782Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00514 in 1,545,466 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0040 ( 2 hom., cov: 34)
Exomes 𝑓: 0.0053 ( 33 hom. )
Consequence
PIEZO1
NM_001142864.4 missense
NM_001142864.4 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 3.99
Genes affected
PIEZO1 (HGNC:28993): (piezo type mechanosensitive ion channel component 1 (Er blood group)) The protein encoded by this gene is a mechanically-activated ion channel that links mechanical forces to biological signals. The encoded protein contains 36 transmembrane domains and functions as a homotetramer. Defects in this gene have been associated with dehydrated hereditary stomatocytosis. [provided by RefSeq, Jul 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.011941671).
BP6
Variant 16-88733731-C-T is Benign according to our data. Variant chr16-88733731-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 242665.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=4}. Variant chr16-88733731-C-T is described in Lovd as [Likely_benign].
BS2
High AC in GnomAd4 at 612 AD,BG gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIEZO1 | NM_001142864.4 | c.2344G>A | p.Gly782Ser | missense_variant | 18/51 | ENST00000301015.14 | NP_001136336.2 | |
HSALR1 | NR_103774.1 | n.269+2283C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIEZO1 | ENST00000301015.14 | c.2344G>A | p.Gly782Ser | missense_variant | 18/51 | 1 | NM_001142864.4 | ENSP00000301015.9 | ||
ENSG00000224888 | ENST00000440406.2 | n.269+2283C>T | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00402 AC: 612AN: 152206Hom.: 2 Cov.: 34
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GnomAD3 exomes AF: 0.00381 AC: 554AN: 145236Hom.: 5 AF XY: 0.00376 AC XY: 293AN XY: 78020
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GnomAD4 exome AF: 0.00526 AC: 7329AN: 1393142Hom.: 33 Cov.: 32 AF XY: 0.00507 AC XY: 3484AN XY: 686826
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GnomAD4 genome AF: 0.00402 AC: 612AN: 152324Hom.: 2 Cov.: 34 AF XY: 0.00361 AC XY: 269AN XY: 74490
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:4Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2Benign:4
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | PIEZO1: BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 02, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 17, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Nov 11, 2022 | BS2, BP4, PP1 - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Jul 31, 2024 | - - |
Lymphatic malformation 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
PIEZO1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 23, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
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