NM_001142864.4:c.7501G>C

Variant names:

• chr16-88715670-C-G
• rs922432809
• NM_001142864.4:c.7501G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001142864.4(PIEZO1):​c.7501G>C​(p.Ala2501Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIEZO1 NM_001142864.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.67

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIEZO1	NM_001142864.4	c.7501G>C	p.Ala2501Pro	missense_variant	Exon 51 of 51	ENST00000301015.14	NP_001136336.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIEZO1	ENST00000301015.14	c.7501G>C	p.Ala2501Pro	missense_variant	Exon 51 of 51	1	NM_001142864.4	ENSP00000301015.9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Benign	0.87
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-4.4	D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.59
MutPred		0.53		Gain of glycosylation at A2501 (P = 0.0232);
MVP		0.29
ClinPred		0.99	D
GERP RS		2.7
Varity_R		0.82
gMVP		0.85

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

LitVar

Other links and lift over

dbSNP: rs922432809; hg19: chr16-88782078;