chr17-3688050-C-A

Variant names:

• chr17-3688050-C-A
• NM_002561.4:c.943G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002561.4(P2RX5):​c.943G>T​(p.Ala315Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. A315T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 28)
• Consequence: P2RX5 NM_002561.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.53

Genes affected

P2RX5 (HGNC:8536): (purinergic receptor P2X 5) The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream gene, TAX1BP3 (Tax1 binding protein 3). [provided by RefSeq, Mar 2011]

P2RX5-TAX1BP3 (HGNC:49191): (P2RX5-TAX1BP3 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring P2RX5 (purinergic receptor P2X, ligand-gated ion channel, 5) and TAX1BP3 (Tax1 binding protein 3) genes on chromosome 17. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.815

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX5	NM_002561.4	c.943G>T	p.Ala315Ser	missense_variant	Exon 9 of 12	ENST00000225328.10	NP_002552.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX5	ENST00000225328.10	c.943G>T	p.Ala315Ser	missense_variant	Exon 9 of 12	1	NM_002561.4	ENSP00000225328.5
P2RX5	ENST00000697413.1	c.943G>T	p.Ala315Ser	missense_variant	Exon 9 of 13			ENSP00000513301.1
P2RX5-TAX1BP3	ENST00000550383.1	n.943G>T		non_coding_transcript_exon_variant	Exon 9 of 15	2		ENSP00000455681.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;.;.;T;.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.82	D;D;D;D;D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.8	.;.;.;M;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.6	.;D;D;D;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.018	.;D;T;D;D;D
Sift4G	Benign	0.10	T;T;T;T;T;T
Polyphen		1.0, 0.99, 0.99, 1.0	.;D;D;D;.;D
Vest4		0.66
MutPred		0.78		.;.;.;Loss of ubiquitination at K314 (P = 0.1516);.;.;
MVP		0.55
MPC		0.53
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.43
gMVP		0.58

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: chr17-3591344;