chr16-88715610-C-G
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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):āc.7561G>Cā(p.Glu2521Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000189 in 1,549,802 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.0010 ( 0 hom., cov: 33)
Exomes š: 0.00010 ( 1 hom. )
Consequence
PIEZO1
NM_001142864.4 missense
NM_001142864.4 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 3.85
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=0.00760749).
BP6
Variant 16-88715610-C-G is Benign according to our data. Variant chr16-88715610-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2041916.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
BS2
High AC in GnomAd4 at 153 AD,BG gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIEZO1 | NM_001142864.4 | c.7561G>C | p.Glu2521Gln | missense_variant | 51/51 | ENST00000301015.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIEZO1 | ENST00000301015.14 | c.7561G>C | p.Glu2521Gln | missense_variant | 51/51 | 1 | NM_001142864.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00101 AC: 154AN: 152178Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000230 AC: 35AN: 152432Hom.: 0 AF XY: 0.000185 AC XY: 15AN XY: 81242
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GnomAD4 exome AF: 0.000100 AC: 140AN: 1397508Hom.: 1 Cov.: 32 AF XY: 0.0000827 AC XY: 57AN XY: 689220
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GnomAD4 genome AF: 0.00100 AC: 153AN: 152294Hom.: 0 Cov.: 33 AF XY: 0.000873 AC XY: 65AN XY: 74460
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 03, 2022 | The c.7561G>C (p.E2521Q) alteration is located in exon 51 (coding exon 51) of the PIEZO1 gene. This alteration results from a G to C substitution at nucleotide position 7561, causing the glutamic acid (E) at amino acid position 2521 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
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