12-121228843-A-T

Variant names:

• chr12-121228843-A-T
• rs25644
• NM_002560.3:c.724A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002560.3(P2RX4):​c.724A>T​(p.Ser242Cys) variant causes a missense 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S242G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: P2RX4 NM_002560.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22

Genes affected

P2RX4 (HGNC:8535): (purinergic receptor P2X 4) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel with high calcium permeability. The main pharmacological distinction between the members of the purinoceptor family is the relative sensitivity to the antagonists suramin and PPADS. The product of this gene has the lowest sensitivity for these antagonists. Multiple alternatively spliced transcript variants, some protein-coding and some not protein-coding, have been found for this gene. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42170876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX4	NM_002560.3	c.724A>T	p.Ser242Cys	missense_variant	Exon 7 of 12	ENST00000337233.9	NP_002551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX4	ENST00000337233.9	c.724A>T	p.Ser242Cys	missense_variant	Exon 7 of 12	1	NM_002560.3	ENSP00000336607.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T;T;.;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.89	D;T;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.42	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;.;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.8	D;.;D;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0050	D;.;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D;D
Polyphen		0.97	D;.;.;.;.
Vest4		0.31
MutPred		0.52		Gain of catalytic residue at S242 (P = 0.0184);Gain of catalytic residue at S242 (P = 0.0184);.;.;.;
MVP		0.66
MPC		0.95
ClinPred		0.98	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs25644; hg19: chr12-121666646;