NM_001142864.4:c.7530G>C

Variant names:

• chr16-88715641-C-G
• NM_001142864.4:c.7530G>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001142864.4(PIEZO1):​c.7530G>C​(p.Pro2510Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,906 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. Synonymous variant affecting the same amino acid position (i.e. P2510P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PIEZO1 NM_001142864.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.68

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02197656).
• BP7: Synonymous conserved (PhyloP=-4.68 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIEZO1	NM_001142864.4	c.7530G>C	p.Pro2510Pro	synonymous_variant	Exon 51 of 51	ENST00000301015.14	NP_001136336.2
CTU2	NM_001012759.3	c.*390C>G		downstream_gene_variant		ENST00000453996.7	NP_001012777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIEZO1	ENST00000301015.14	c.7530G>C	p.Pro2510Pro	synonymous_variant	Exon 51 of 51	1	NM_001142864.4	ENSP00000301015.9
CTU2	ENST00000453996.7	c.*390C>G		downstream_gene_variant		1	NM_001012759.3	ENSP00000388320.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397906 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 689454

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.0029	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	0.0040
DANN	Benign	0.77
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.95	T
PROVEAN	Benign	2.3	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.16
MutPred		0.16		Loss of relative solvent accessibility (P = 0.0404);
MVP		0.043
ClinPred		0.15	T
GERP RS		-9.5

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-88782049;