17-3676358-T-C

Variant names:

• chr17-3676358-T-C
• rs149245
• NM_002561.4:c.1260-2481A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002561.4(P2RX5):​c.1260-2481A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 984,580 control chromosomes in the GnomAD database, including 84,288 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (18029 hom., cov: 32)
  • Exomes 𝑓: 0.40 (66259 hom.)
• Consequence: P2RX5 NM_002561.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX5	NM_002561.4	c.1260-2481A>G		intron_variant	Intron 11 of 11	ENST00000225328.10	NP_002552.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX5	ENST00000225328.10	c.1260-2481A>G		intron_variant	Intron 11 of 11	1	NM_002561.4	ENSP00000225328.5
P2RX5	ENST00000697413.1	c.1326-2481A>G		intron_variant	Intron 12 of 12			ENSP00000513301.1
P2RX5-TAX1BP3	ENST00000550383.1	n.1259+3232A>G		intron_variant	Intron 11 of 14	2		ENSP00000455681.1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71530 AN: 151934 Hom.: 18011 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.396 AC: 330036 AN: 832528 Hom.: 66259 Cov.: 32 AF XY: 0.397 AC XY: 152702 AN XY: 384478

African (AFR) AF: 0.676 AC: 10669 AN: 15780

American (AMR) AF: 0.436 AC: 429 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 2157 AN: 5148

East Asian (EAS) AF: 0.556 AC: 2019 AN: 3630

South Asian (SAS) AF: 0.464 AC: 7620 AN: 16440

European-Finnish (FIN) AF: 0.311 AC: 87 AN: 280

Middle Eastern (MID) AF: 0.444 AC: 718 AN: 1618

European-Non Finnish (NFE) AF: 0.387 AC: 294648 AN: 761368

Other (OTH) AF: 0.428 AC: 11689 AN: 27280

GnomAD4 genome AF: 0.471 AC: 71604 AN: 152052 Hom.: 18029 Cov.: 32 AF XY: 0.468 AC XY: 34780 AN XY: 74328

African (AFR) AF: 0.646 AC: 26783 AN: 41478

American (AMR) AF: 0.475 AC: 7254 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1448 AN: 3470

East Asian (EAS) AF: 0.543 AC: 2806 AN: 5166

South Asian (SAS) AF: 0.458 AC: 2207 AN: 4824

European-Finnish (FIN) AF: 0.296 AC: 3127 AN: 10562

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26514 AN: 67962

Other (OTH) AF: 0.457 AC: 966 AN: 2114

Alfa AF: 0.398 Hom.: 2531

Bravo AF: 0.493

Asia WGS AF: 0.499 AC: 1737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.3
DANN	Benign	0.57
PhyloP100		-0.061
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs149245; hg19: chr17-3579652;