chr16-88715442-C-T

Variant names:

• chr16-88715442-C-T
• rs1061238
• NM_001142864.4:c.*163G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.30
• Publications: 13 publications found

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]

CTU2 Gene-Disease associations (from GenCC):

• microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1246797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIEZO1	NM_001142864.4	MANE Select	c.*163G>A		3_prime_UTR	Exon 51 of 51	NP_001136336.2	Q92508
	CTU2	NM_001012759.3	MANE Select	c.*191C>T		downstream_gene	N/A	NP_001012777.1	Q2VPK5-1
	CTU2	NM_001318507.2		c.*191C>T		downstream_gene	N/A	NP_001305436.1	H3BSW6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIEZO1	ENST00000301015.14	TSL:1 MANE Select	c.*163G>A		3_prime_UTR	Exon 51 of 51	ENSP00000301015.9	Q92508
	PIEZO1	ENST00000419505.5	TSL:1	n.*1269G>A		non_coding_transcript_exon	Exon 10 of 10	ENSP00000406358.1	H7C2J5
	PIEZO1	ENST00000419505.5	TSL:1	n.*1269G>A		3_prime_UTR	Exon 10 of 10	ENSP00000406358.1	H7C2J5

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

African (AFR) AF: 0.0638 AC: 1234 AN: 19340

American (AMR) AF: 0.0405 AC: 1019 AN: 25172

Ashkenazi Jewish (ASJ) AF: 0.0953 AC: 1607 AN: 16856

East Asian (EAS) AF: 0.000213 AC: 7 AN: 32934

South Asian (SAS) AF: 0.0306 AC: 1677 AN: 54810

European-Finnish (FIN) AF: 0.160 AC: 4878 AN: 30554

Middle Eastern (MID) AF: 0.0255 AC: 68 AN: 2664

European-Non Finnish (NFE) AF: 0.148 AC: 83247 AN: 563738

Other (OTH) AF: 0.103 AC: 3826 AN: 37172

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

African (AFR) AF: 0.0657 AC: 2728 AN: 41544

American (AMR) AF: 0.0452 AC: 692 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0954 AC: 331 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0247 AC: 119 AN: 4824

European-Finnish (FIN) AF: 0.146 AC: 1549 AN: 10602

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9553 AN: 67990

Other (OTH) AF: 0.0742 AC: 157 AN: 2116

Alfa AF: 0.125 Hom.: 195

Bravo AF: 0.0914

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1061238; hg19: chr16-88781850;