chr16-88715649-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001142864.4(PIEZO1):​c.7522C>A​(p.Arg2508Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R2508R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

PIEZO1
NM_001142864.4 missense

Scores

8
2
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.85
Variant links:
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIEZO1NM_001142864.4 linkuse as main transcriptc.7522C>A p.Arg2508Ser missense_variant 51/51 ENST00000301015.14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIEZO1ENST00000301015.14 linkuse as main transcriptc.7522C>A p.Arg2508Ser missense_variant 51/511 NM_001142864.4 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesMar 29, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Benign
-0.064
T
BayesDel_noAF
Pathogenic
0.37
CADD
Pathogenic
30
DANN
Benign
0.95
Eigen
Pathogenic
0.94
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.33
T
M_CAP
Pathogenic
0.89
D
MetaRNN
Uncertain
0.46
T
MetaSVM
Pathogenic
1.2
D
MutationTaster
Benign
1.0
D;D
PROVEAN
Benign
0.78
N
REVEL
Uncertain
0.36
Sift
Pathogenic
0.0
D
Polyphen
0.99
D
Vest4
0.37
MutPred
0.14
Loss of loop (P = 0.0603);
MVP
0.28
ClinPred
1.0
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-88782057; API