Variant 16-88725505-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001142864.4(PIEZO1):c.4073G>A(p.Arg1358His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000085 in 1,529,108 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000087 ( 0 hom. )

Consequence

PIEZO1
NM_001142864.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

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]

PIEZO1 links:

PIEZO1 (HGNC:):

PIEZO1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 12 AD,BG gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIEZO1	NM_001142864.4 linkuse as main transcript	c.4073G>A	p.Arg1358His	missense_variant	29/51	ENST00000301015.14	NP_001136336.2	Q92508

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PIEZO1	ENST00000301015.14 linkuse as main transcript	c.4073G>A	p.Arg1358His	missense_variant	29/51	1	NM_001142864.4	ENSP00000301015.9	Q92508
PIEZO1	ENST00000474606.1 linkuse as main transcript	c.164G>A	p.Arg55His	missense_variant	3/7	4		ENSP00000428673.1	H0YB49
PIEZO1	ENST00000475586.1 linkuse as main transcript	n.446G>A		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000871

AC:

AN:

1377054

Hom.:

Cov.:

AF XY:

0.0000118

AC XY:

AN XY:

677124

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000783

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000563

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.56

Eigen

Benign

0.030

Eigen_PC

Benign

0.000085

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.87

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.39

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.33

MutPred

0.24

Gain of methylation at K1360 (P = 0.0446);

MVP

0.58

ClinPred

0.97

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over