Variant X-70258681-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002565.4(P2RY4):c.944G>A(p.Arg315His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,097,885 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000064 ( 0 hom. 4 hem. )

Consequence

P2RY4
NM_002565.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.774

Variant links:

Genes affected

P2RY4 (HGNC:8542): (pyrimidinergic receptor P2Y4) The product of this gene belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is responsive to uridine nucleotides, partially responsive to ATP, and not responsive to ADP. [provided by RefSeq, Jul 2008]

P2RY4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07981324).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RY4	NM_002565.4 linkuse as main transcript	c.944G>A	p.Arg315His	missense_variant	1/1	ENST00000374519.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RY4	ENST00000374519.4 linkuse as main transcript	c.944G>A	p.Arg315His	missense_variant	1/1		NM_002565.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

181948

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

66492

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000725

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000638

AC:

AN:

1097885

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363247

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 24, 2024

The c.944G>A (p.R315H) alteration is located in exon 1 (coding exon 1) of the P2RY4 gene. This alteration results from a G to A substitution at nucleotide position 944, causing the arginine (R) at amino acid position 315 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.094

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.73

M_CAP

Benign

0.0045

MetaRNN

Benign

0.080

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.7

REVEL

Benign

0.0090

Sift

Benign

0.052

Sift4G

Uncertain

0.013

Polyphen

0.26

Vest4

0.089

MutPred

0.40

Loss of MoRF binding (P = 0.0133);

MVP

0.67

MPC

0.10

ClinPred

0.19

GERP RS

3.3

Varity_R

0.079

gMVP

0.24

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over