rs3215407

Variant names:

• chr17-3690982-TGGGG-T
• rs3215407
• NM_002561.4:c.330_333delCCCC

Your query was ambiguous. Multiple possible variants found:

• chr17-3690982-TGGGG-T
• chr17-3690982-TGGGG-TGG
• chr17-3690982-TGGGG-TGGG
• chr17-3690982-TGGGG-TGGGGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002561.4(P2RX5):​c.330_333delCCCC​(p.Pro111ThrfsTer36) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000685 in 1,460,376 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: P2RX5 NM_002561.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.47
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.330_333delCCCC	p.Pro111ThrfsTer36	frameshift	Exon 3 of 12	NP_002552.2
	P2RX5	NM_001204519.2		c.330_333delCCCC	p.Pro111ThrfsTer36	frameshift	Exon 3 of 12	NP_001191448.1	Q93086-1
	P2RX5	NM_001425082.1		c.-295_-292delCCCC		5_prime_UTR	Exon 6 of 15	NP_001412011.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RX5	ENST00000225328.10	TSL:1 MANE Select	c.330_333delCCCC	p.Pro111ThrfsTer36	frameshift	Exon 3 of 12	ENSP00000225328.5	Q93086-3
	P2RX5	ENST00000697413.1		c.330_333delCCCC	p.Pro111ThrfsTer36	frameshift	Exon 3 of 13	ENSP00000513301.1	Q93086-6
	P2RX5	ENST00000547178.5	TSL:1	c.330_333delCCCC	p.Pro111ThrfsTer36	frameshift	Exon 3 of 12	ENSP00000448355.1	Q93086-1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460376 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 726438

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111440

Other (OTH) AF: 0.00 AC: 0 AN: 60368

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5

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: rs3215407; hg19: chr17-3594276;