chr17-3898140-G-C

Variant names:

• chr17-3898140-G-C
• rs149912938
• NM_002558.4:c.1033-30C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002558.4(P2RX1):​c.1033-30C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,434,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: P2RX1 NM_002558.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940

Genes affected

P2RX1 (HGNC:8533): (purinergic receptor P2X 1) The protein encoded by this gene belongs to the P2X family of G-protein-coupled receptors. These proteins can form homo-and heterotimers and function as ATP-gated ion channels and mediate rapid and selective permeability to cations. This protein is primarily localized to smooth muscle where binds ATP and mediates synaptic transmission between neurons and from neurons to smooth muscle and may being responsible for sympathetic vasoconstriction in small arteries, arterioles and vas deferens. Mouse studies suggest that this receptor is essential for normal male reproductive function. This protein may also be involved in promoting apoptosis. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RX1	NM_002558.4	c.1033-30C>G		intron_variant	Intron 10 of 11	ENST00000225538.4	NP_002549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RX1	ENST00000225538.4	c.1033-30C>G		intron_variant	Intron 10 of 11	1	NM_002558.4	ENSP00000225538.3
P2RX1	ENST00000572418.1	n.1556-30C>G		intron_variant	Intron 9 of 10	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.00000799 AC: 2 AN: 250244 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135428

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000279 AC: 4 AN: 1434708 Hom.: 0 Cov.: 26 AF XY: 0.00000280 AC XY: 2 AN XY: 715488

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000467

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.6
DANN	Benign	0.62
BranchPoint Hunter		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: -1

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

Publications

LitVar

Other links and lift over

dbSNP: rs149912938; hg19: chr17-3801434;