16-88715442-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142864.4(PIEZO1):​c.*163G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PIEZO1 NM_001142864.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

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>C		3_prime_UTR	Exon 51 of 51	NP_001136336.2	Q92508
	CTU2	NM_001012759.3	MANE Select	c.*191C>G		downstream_gene	N/A	NP_001012777.1	Q2VPK5-1
	CTU2	NM_001318507.2		c.*191C>G		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>C		3_prime_UTR	Exon 51 of 51	ENSP00000301015.9	Q92508
	PIEZO1	ENST00000419505.5	TSL:1	n.*1269G>C		non_coding_transcript_exon	Exon 10 of 10	ENSP00000406358.1	H7C2J5
	PIEZO1	ENST00000419505.5	TSL:1	n.*1269G>C		3_prime_UTR	Exon 10 of 10	ENSP00000406358.1	H7C2J5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 783942 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 398542

African (AFR) AF: 0.00 AC: 0 AN: 19350

American (AMR) AF: 0.00 AC: 0 AN: 25172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16862

East Asian (EAS) AF: 0.00 AC: 0 AN: 32934

South Asian (SAS) AF: 0.00 AC: 0 AN: 54810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2664

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 564410

Other (OTH) AF: 0.00 AC: 0 AN: 37186

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		1.3

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;