17-3688050-C-T

Variant names:

• chr17-3688050-C-T
• rs148409834
• NM_002561.4:c.943G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002561.4(P2RX5):​c.943G>A​(p.Ala315Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000411 in 1,604,598 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: P2RX5 NM_002561.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.53
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002561.4. 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
	P2RX5	NM_002561.4	MANE Select	c.943G>A	p.Ala315Thr	missense	Exon 9 of 12	NP_002552.2
	P2RX5	NM_001204519.2		c.940G>A	p.Ala314Thr	missense	Exon 9 of 12	NP_001191448.1	Q93086-1
	P2RX5	NM_001204520.2		c.871G>A	p.Ala291Thr	missense	Exon 8 of 11	NP_001191449.1	Q93086-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX5	ENST00000225328.10	TSL:1 MANE Select	c.943G>A	p.Ala315Thr	missense	Exon 9 of 12	ENSP00000225328.5	Q93086-3
	P2RX5	ENST00000697413.1		c.943G>A	p.Ala315Thr	missense	Exon 9 of 13	ENSP00000513301.1	Q93086-6
	P2RX5	ENST00000547178.5	TSL:1	c.940G>A	p.Ala314Thr	missense	Exon 9 of 12	ENSP00000448355.1	Q93086-1

Frequencies

GnomAD3 genomes AF: 0.000174 AC: 26 AN: 149118 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00140

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000744

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000949 AC: 23 AN: 242344 AF XY: 0.000107

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000529

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000458

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000275 AC: 40 AN: 1455480 Hom.: 0 Cov.: 30 AF XY: 0.0000345 AC XY: 25 AN XY: 723714

African (AFR) AF: 0.00 AC: 0 AN: 33292

American (AMR) AF: 0.000361 AC: 16 AN: 44332

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39352

South Asian (SAS) AF: 0.00 AC: 0 AN: 85166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1108728

Other (OTH) AF: 0.0000166 AC: 1 AN: 60074

GnomAD4 genome AF: 0.000174 AC: 26 AN: 149118 Hom.: 0 Cov.: 28 AF XY: 0.000248 AC XY: 18 AN XY: 72610

African (AFR) AF: 0.00 AC: 0 AN: 40368

American (AMR) AF: 0.00140 AC: 21 AN: 14996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 4970

South Asian (SAS) AF: 0.00 AC: 0 AN: 4580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000744 AC: 5 AN: 67226

Other (OTH) AF: 0.00 AC: 0 AN: 2036

Alfa AF: 0.0000902 Hom.: 0

Bravo AF: 0.000162

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	0.31	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.5
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.027	D
Polyphen		0.99	D
Vest4		0.69
MVP		0.61
MPC		0.57
ClinPred		0.64	D
GERP RS		5.1
Varity_R		0.45
gMVP		0.57
Mutation Taster		=67/33	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: rs148409834; hg19: chr17-3591344;