16-88715442-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001142864.4(PIEZO1):c.*163G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 935,476 control chromosomes in the GnomAD database, including 8,056 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (910 hom., cov: 33)
  • Exomes 𝑓: 0.12 (7146 hom.)
• Consequence: PIEZO1 NM_001142864.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.30

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 16-88715442-C-T is Benign according to our data. Variant chr16-88715442-C-T is described in ClinVar as [Benign]. Clinvar id is 1246797.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIEZO1	NM_001142864.4	c.*163G>A		3_prime_UTR_variant	51/51	ENST00000301015.14
CTU2	NM_001012759.3			downstream_gene_variant		ENST00000453996.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIEZO1	ENST00000301015.14	c.*163G>A		3_prime_UTR_variant	51/51	1	NM_001142864.4	P1
CTU2	ENST00000453996.7			downstream_gene_variant		1	NM_001012759.3	P2

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15198 AN: 152122 Hom.: 908 Cov.: 33

Gnomad AFR AF: 0.0655

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0453

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0246

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.0755

GnomAD4 exome AF: 0.125 AC: 97563 AN: 783240 Hom.: 7146 Cov.: 10 AF XY: 0.121 AC XY: 48084 AN XY: 398194

Gnomad4 AFR exome AF: 0.0638

Gnomad4 AMR exome AF: 0.0405

Gnomad4 ASJ exome AF: 0.0953

Gnomad4 EAS exome AF: 0.000213

Gnomad4 SAS exome AF: 0.0306

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.0999 AC: 15208 AN: 152236 Hom.: 910 Cov.: 33 AF XY: 0.0966 AC XY: 7192 AN XY: 74436

Gnomad4 AFR AF: 0.0657

Gnomad4 AMR AF: 0.0452

Gnomad4 ASJ AF: 0.0954

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0247

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.0742

Alfa AF: 0.125 Hom.: 195

Bravo AF: 0.0914

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	12
Dann	Benign	0.91

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

Other links and lift over

dbSNP: rs1061238; hg19: chr16-88781850;