NM_014879.4:c.440T>C

Variant names:

• chr3-151213877-A-G
• NM_014879.4:c.440T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014879.4(P2RY14):​c.440T>C​(p.Met147Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: -0.726

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16728961).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RY14	NM_014879.4	c.440T>C	p.Met147Thr	missense_variant	Exon 3 of 3	ENST00000309170.8	NP_055694.3
MED12L	NM_001393769.1	c.2250+20211A>G		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.440T>C	p.Met147Thr	missense_variant	Exon 3 of 3	1	NM_014879.4	ENSP00000308361.3
MED12L	ENST00000687756.1	c.2250+20211A>G		intron_variant	Intron 16 of 44		NM_001393769.1	ENSP00000508695.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.440T>C (p.M147T) alteration is located in exon 3 (coding exon 1) of the P2RY14 gene. This alteration results from a T to C substitution at nucleotide position 440, causing the methionine (M) at amino acid position 147 to be replaced by a threonine (T). 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	0.093
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.24
DANN	Benign	0.54
DEOGEN2	Benign	0.053	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.37	.;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.19	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.20	N;N
REVEL	Benign	0.060
Sift	Benign	0.25	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.0	B;B
Vest4		0.083
MutPred		0.65		Loss of stability (P = 0.103);Loss of stability (P = 0.103);
MVP		0.19
MPC		0.061
ClinPred		0.30	T
GERP RS		-4.7
Varity_R		0.050
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-150931665;