rs1061247

Variant names:

• chr16-88715383-A-C
• rs1061247
• NM_001142864.4:c.*222T>G

Your query was ambiguous. Multiple possible variants found:

• chr16-88715383-A-C
• chr16-88715383-A-G

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.*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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00
• Publications: 11 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.*222T>G		3_prime_UTR	Exon 51 of 51	NP_001136336.2	Q92508
	CTU2	NM_001012759.3	MANE Select	c.*132A>C		3_prime_UTR	Exon 15 of 15	NP_001012777.1	Q2VPK5-1
	CTU2	NM_001318507.2		c.*132A>C		3_prime_UTR	Exon 15 of 15	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.*222T>G		3_prime_UTR	Exon 51 of 51	ENSP00000301015.9	Q92508
	CTU2	ENST00000453996.7	TSL:1 MANE Select	c.*132A>C		3_prime_UTR	Exon 15 of 15	ENSP00000388320.2	Q2VPK5-1
	CTU2	ENST00000567949.5	TSL:1	c.*132A>C		3_prime_UTR	Exon 15 of 15	ENSP00000456908.1	H3BSW6

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22015 AN: 152078 Hom.: 1786 Cov.: 33

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.: 13 AF XY: 0.136 AC XY: 65866 AN XY: 486080

African (AFR) AF: 0.218 AC: 4812 AN: 22030

American (AMR) AF: 0.0566 AC: 1224 AN: 21610

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 1900 AN: 18264

East Asian (EAS) AF: 0.0578 AC: 1953 AN: 33788

South Asian (SAS) AF: 0.0528 AC: 3121 AN: 59078

European-Finnish (FIN) AF: 0.161 AC: 5028 AN: 31288

Middle Eastern (MID) AF: 0.0453 AC: 137 AN: 3024

European-Non Finnish (NFE) AF: 0.150 AC: 110734 AN: 736088

Other (OTH) AF: 0.123 AC: 5297 AN: 43228

GnomAD4 genome AF: 0.145 AC: 22044 AN: 152196 Hom.: 1793 Cov.: 33 AF XY: 0.141 AC XY: 10503 AN XY: 74408

African (AFR) AF: 0.205 AC: 8521 AN: 41490

American (AMR) AF: 0.0636 AC: 973 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3472

East Asian (EAS) AF: 0.0569 AC: 295 AN: 5182

South Asian (SAS) AF: 0.0511 AC: 247 AN: 4834

European-Finnish (FIN) AF: 0.146 AC: 1553 AN: 10608

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9767 AN: 67986

Other (OTH) AF: 0.110 AC: 232 AN: 2114

Alfa AF: 0.155 Hom.: 285

Bravo AF: 0.142

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.49
CADD	Benign	7.1
DANN	Benign	0.88
PhyloP100		0.0
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: rs1061247; hg19: chr16-88781791; COSMIC: COSV105157837; COSMIC: COSV105157837;