chr3-151213455-C-T

Variant names:

• chr3-151213455-C-T
• rs1727536937
• NM_014879.4:c.862G>A

Variant summary

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

The NM_014879.4(P2RY14):​c.862G>A​(p.Val288Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: P2RY14 NM_014879.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06

Genes affected

P2RY14 (HGNC:16442): (purinergic receptor P2Y14) The product of this gene belongs to the family of G-protein coupled receptors, which contains several receptor subtypes with different pharmacological selectivity for various adenosine and uridine nucleotides. This receptor is a P2Y purinergic receptor for UDP-glucose and other UDP-sugars coupled to G-proteins. It has been implicated in extending the known immune system functions of P2Y receptors by participating in the regulation of the stem cell compartment, and it may also play a role in neuroimmune function. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]

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
P2RY14	NM_014879.4	c.862G>A	p.Val288Ile	missense_variant	Exon 3 of 3	ENST00000309170.8	NP_055694.3
MED12L	NM_001393769.1	c.2250+19789C>T		intron_variant	Intron 16 of 44	ENST00000687756.1	NP_001380698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RY14	ENST00000309170.8	c.862G>A	p.Val288Ile	missense_variant	Exon 3 of 3	1	NM_014879.4	ENSP00000308361.3
MED12L	ENST00000687756.1	c.2250+19789C>T		intron_variant	Intron 16 of 44		NM_001393769.1	ENSP00000508695.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.862G>A (p.V288I) alteration is located in exon 3 (coding exon 1) of the P2RY14 gene. This alteration results from a G to A substitution at nucleotide position 862, causing the valine (V) at amino acid position 288 to be replaced by an isoleucine (I). 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	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T;T
Eigen	Benign	0.078
Eigen_PC	Benign	-0.062
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.70	.;T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.40	N;N
REVEL	Uncertain	0.30
Sift	Benign	0.31	T;T
Sift4G	Benign	0.26	T;T
Polyphen		1.0	D;D
Vest4		0.099
MutPred		0.53		Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.72
MPC		0.15
ClinPred		0.51	D
GERP RS		3.6
Varity_R		0.079
gMVP		0.44

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

Other links and lift over

dbSNP: rs1727536937; hg19: chr3-150931243;