Variant 16-88715383-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142864.4(PIEZO1):c.*222T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,120,594 control chromosomes in the GnomAD database, including 12,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1793 hom., cov: 33)

Exomes 𝑓: 0.14 ( 10579 hom. )

Consequence

PIEZO1
NM_001142864.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00

Variant links:

Genes affected

CTU2 (HGNC:28005): (cytosolic thiouridylase subunit 2) This gene encodes a protein which is involved in the post-transcriptional modification of transfer RNAs (tRNAs). The encoded protein plays a role in thiolation of uridine residue present at the wobble position in a subset of tRNAs, resulting in enhanced codon reading accuracy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

CTU2 links:

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 16-88715383-A-C is Benign according to our data. Variant chr16-88715383-A-C is described in ClinVar as [Benign]. Clinvar id is 1252833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTU2	NM_001012759.3 linkuse as main transcript	c.*132A>C		3_prime_UTR_variant	15/15	ENST00000453996.7
PIEZO1	NM_001142864.4 linkuse as main transcript	c.*222T>G		3_prime_UTR_variant	51/51	ENST00000301015.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO1	ENST00000301015.14 linkuse as main transcript	c.*222T>G		3_prime_UTR_variant	51/51	1	NM_001142864.4	P1
CTU2	ENST00000453996.7 linkuse as main transcript	c.*132A>C		3_prime_UTR_variant	15/15	1	NM_001012759.3	P2	Q2VPK5-1

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22015

AN:

152078

Hom.:

1786

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.0824

Gnomad AMR

AF:

0.0637

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.0574

Gnomad SAS

AF:

0.0513

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.109

GnomAD4 exome

AF:

0.139

AC:

134206

AN:

968398

Hom.:

10579

Cov.:

AF XY:

0.136

AC XY:

65866

AN XY:

486080

show subpopulations

Gnomad4 AFR exome

AF:

0.218

Gnomad4 AMR exome

AF:

0.0566

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.0578

Gnomad4 SAS exome

AF:

0.0528

Gnomad4 FIN exome

AF:

0.161

Gnomad4 NFE exome

AF:

0.150

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.145

AC:

22044

AN:

152196

Hom.:

1793

Cov.:

AF XY:

0.141

AC XY:

10503

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.205

Gnomad4 AMR

AF:

0.0636

Gnomad4 ASJ

AF:

0.106

Gnomad4 EAS

AF:

0.0569

Gnomad4 SAS

AF:

0.0511

Gnomad4 FIN

AF:

0.146

Gnomad4 NFE

AF:

0.144

Gnomad4 OTH

AF:

0.110

Alfa

AF:

0.155

Hom.:

285

Bravo

AF:

0.142

Asia WGS

AF:

0.0800

AC:

278

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.1

DANN

Benign

0.88

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over