GeneBe

rs869025596

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_001142864.4(PIEZO1):​c.2263G>T​(p.Glu755*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PIEZO1
NM_001142864.4 stop_gained

Scores

2
2
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.480

Publications

4 publications found
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]
HSALR1 (HGNC:56095): (HSP90AB1 associated lncRNA 1)

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 11 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-88733972-C-A is Pathogenic according to our data. Variant chr16-88733972-C-A is described in ClinVar as Pathogenic. ClinVar VariationId is 223127.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142864.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PIEZO1
NM_001142864.4
MANE Select
c.2263G>Tp.Glu755*
stop_gained
Exon 17 of 51NP_001136336.2
HSALR1
NR_103774.1
n.269+2524C>A
intron
N/A

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PIEZO1
ENST00000301015.14
TSL:1 MANE Select
c.2263G>Tp.Glu755*
stop_gained
Exon 17 of 51ENSP00000301015.9
HSALR1
ENST00000440406.2
TSL:2
n.269+2524C>A
intron
N/A

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1395936
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
688354
African (AFR)
AF:
0.00
AC:
0
AN:
31364
American (AMR)
AF:
0.00
AC:
0
AN:
35612
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25108
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35692
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79100
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
47842
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5652
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1077644
Other (OTH)
AF:
0.00
AC:
0
AN:
57922
GnomAD4 genome
Cov.:
33

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic
Revision:no assertion criteria provided
View on ClinVar
Pathogenic
VUS
Benign
Condition
1
-
-
Lymphatic malformation 6 (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.51
CADD
Pathogenic
36
DANN
Uncertain
1.0
Eigen
Uncertain
0.50
Eigen_PC
Benign
0.20
FATHMM_MKL
Benign
0.51
D
PhyloP100
-0.48
Vest4
0.38
ClinPred
0.97
D
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.3
Mutation Taster
=10/190
disease causing (ClinVar)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs869025596; hg19: chr16-88800380; API