3-151213829-C-G

Variant names:

• chr3-151213829-C-G
• rs774718365
• NM_014879.4:c.488G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014879.4(P2RY14):​c.488G>C​(p.Ser163Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S163N) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: P2RY14 NM_014879.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901
• Publications: 0 publications found

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]

MED12L Gene-Disease associations (from GenCC):

• Nizon-Isidor syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045483977).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014879.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RY14	NM_014879.4	MANE Select	c.488G>C	p.Ser163Thr	missense	Exon 3 of 3	NP_055694.3
	MED12L	NM_001393769.1	MANE Select	c.2250+20163C>G		intron	N/A	NP_001380698.1	A0A8I5KX78
	P2RY14	NM_001081455.2		c.488G>C	p.Ser163Thr	missense	Exon 3 of 3	NP_001074924.1	A5JUU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P2RY14	ENST00000309170.8	TSL:1 MANE Select	c.488G>C	p.Ser163Thr	missense	Exon 3 of 3	ENSP00000308361.3	Q15391
	MED12L	ENST00000687756.1	MANE Select	c.2250+20163C>G		intron	N/A	ENSP00000508695.1	A0A8I5KX78
	MED12L	ENST00000474524.5	TSL:1	c.2145+20163C>G		intron	N/A	ENSP00000417235.1	Q86YW9-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.1
DANN	Benign	0.63
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.41	N
PhyloP100		-0.90
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.094
Sift	Benign	0.50	T
Sift4G	Benign	0.55	T
Polyphen		0.019	B
Vest4		0.082
MutPred		0.47		Gain of catalytic residue at S163 (P = 0.0398)
MVP		0.20
MPC		0.052
ClinPred		0.032	T
GERP RS		0.81
Varity_R		0.083
gMVP		0.15
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs774718365; hg19: chr3-150931617;