17-3679765-G-A

Variant names:

• chr17-3679765-G-A
• rs143675939
• NM_002561.4:c.1084C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The NM_002561.4(P2RX5):​c.1084C>T​(p.Gln362*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00078 in 1,611,090 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0033 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00051 (3 hom.)
• Consequence: P2RX5 NM_002561.4 stop_gained
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.270
• Publications: 8 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: Likely_benign. The variant received -5 ACMG points.

• BP6: Variant 17-3679765-G-A is Benign according to our data. Variant chr17-3679765-G-A is described in ClinVar as Benign. ClinVar VariationId is 3050460.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.1084C>T	p.Gln362*	stop_gained	Exon 11 of 12	NP_002552.2
	P2RX5	NM_001204519.2		c.1081C>T	p.Gln361*	stop_gained	Exon 11 of 12	NP_001191448.1	Q93086-1
	P2RX5	NM_001204520.2		c.1012C>T	p.Gln338*	stop_gained	Exon 10 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.1084C>T	p.Gln362*	stop_gained	Exon 11 of 12	ENSP00000225328.5	Q93086-3
	P2RX5	ENST00000697413.1		c.1150C>T	p.Gln384*	stop_gained	Exon 12 of 13	ENSP00000513301.1	Q93086-6
	P2RX5	ENST00000547178.5	TSL:1	c.1081C>T	p.Gln361*	stop_gained	Exon 11 of 12	ENSP00000448355.1	Q93086-1

Frequencies

GnomAD3 genomes AF: 0.00333 AC: 506 AN: 152076 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00122 AC: 304 AN: 248962 AF XY: 0.000861

Gnomad AFR exome AF: 0.0126

Gnomad AMR exome AF: 0.00211

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000512 AC: 747 AN: 1458896 Hom.: 3 Cov.: 32 AF XY: 0.000461 AC XY: 335 AN XY: 725904

African (AFR) AF: 0.0123 AC: 410 AN: 33456

American (AMR) AF: 0.00181 AC: 81 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50756

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.000175 AC: 195 AN: 1111798

Other (OTH) AF: 0.000911 AC: 55 AN: 60362

GnomAD4 genome AF: 0.00334 AC: 509 AN: 152194 Hom.: 5 Cov.: 33 AF XY: 0.00359 AC XY: 267 AN XY: 74402

African (AFR) AF: 0.0110 AC: 457 AN: 41498

American (AMR) AF: 0.00203 AC: 31 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67978

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00172 Hom.: 2

Bravo AF: 0.00365

ESP6500AA AF: 0.00885 AC: 39

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00120 AC: 146

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	P2RX5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	34
DANN	Benign	0.96
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.088	N
PhyloP100		0.27
Vest4		0.47
ClinPred		0.14	T
GERP RS		0.84
Mutation Taster		=194/6	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: 19

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs143675939; hg19: chr17-3583059;