NM_001142864.4:c.*222T>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001142864.4(PIEZO1):​c.*222T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000103 in 969,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: PIEZO1 NM_001142864.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000103 AC: 1 AN: 969116 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 486408

African (AFR) AF: 0.00 AC: 0 AN: 22042

American (AMR) AF: 0.00 AC: 0 AN: 21610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18266

East Asian (EAS) AF: 0.00 AC: 0 AN: 33792

South Asian (SAS) AF: 0.00 AC: 0 AN: 59090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3024

European-Non Finnish (NFE) AF: 0.00000136 AC: 1 AN: 736748

Other (OTH) AF: 0.00 AC: 0 AN: 43248

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.8
DANN	Benign	0.87
PhyloP100		0.0

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;