chrX-70259255-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002565.4(P2RY4):c.370C>T(p.Leu124Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,211,279 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 55 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., 5 hem., cov: 24)
Exomes 𝑓: 0.00014 ( 0 hom. 50 hem. )
Consequence
P2RY4
NM_002565.4 missense
NM_002565.4 missense
Scores
6
11
Clinical Significance
Conservation
PhyloP100: 2.49
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]
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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=0.22495705).
BS2
High Hemizygotes in GnomAd4 at 5 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
P2RY4 | NM_002565.4 | c.370C>T | p.Leu124Phe | missense_variant | 1/1 | ENST00000374519.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
P2RY4 | ENST00000374519.4 | c.370C>T | p.Leu124Phe | missense_variant | 1/1 | NM_002565.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 20AN: 113193Hom.: 0 Cov.: 24 AF XY: 0.000142 AC XY: 5AN XY: 35321
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000137 AC: 25AN: 183033Hom.: 0 AF XY: 0.000119 AC XY: 8AN XY: 67501
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GnomAD4 exome AF: 0.000136 AC: 149AN: 1098086Hom.: 0 Cov.: 32 AF XY: 0.000138 AC XY: 50AN XY: 363442
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GnomAD4 genome AF: 0.000177 AC: 20AN: 113193Hom.: 0 Cov.: 24 AF XY: 0.000142 AC XY: 5AN XY: 35321
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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 | Jun 02, 2023 | The c.370C>T (p.L124F) alteration is located in exon 1 (coding exon 1) of the P2RY4 gene. This alteration results from a C to T substitution at nucleotide position 370, causing the leucine (L) at amino acid position 124 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at