rs922432809

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-88715670-C-G
• chr16-88715670-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2501T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIEZO1 NM_001142864.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.67
• Publications: 1 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]

PIEZO1 Gene-Disease associations (from GenCC):

• PIEZO1-related generalized lymphatic dysplasia with non-immune hydrops fetalis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema

  Inheritance: AD Classification: STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• lymphatic malformation 6

  Inheritance: AR Classification: STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• dehydrated hereditary stomatocytosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.7501G>C	p.Ala2501Pro	missense	Exon 51 of 51	NP_001136336.2	Q92508

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIEZO1	ENST00000301015.14	TSL:1 MANE Select	c.7501G>C	p.Ala2501Pro	missense	Exon 51 of 51	ENSP00000301015.9	Q92508
	PIEZO1	ENST00000419505.5	TSL:1	n.*1041G>C		non_coding_transcript_exon	Exon 10 of 10	ENSP00000406358.1	H7C2J5
	PIEZO1	ENST00000419505.5	TSL:1	n.*1041G>C		3_prime_UTR	Exon 10 of 10	ENSP00000406358.1	H7C2J5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		4.7
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
Mutation Taster		=60/40	polymorphism

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: rs922432809; hg19: chr16-88782078;