3-151213415-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014879.4(P2RY14):c.902C>T(p.Pro301Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,613,982 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (38 hom.)
• Consequence: P2RY14 NM_014879.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.50

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012921363).
• BP6: Variant 3-151213415-G-A is Benign according to our data. Variant chr3-151213415-G-A is described in ClinVar as [Benign]. Clinvar id is 729312.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00186 (283/152248) while in subpopulation EAS AF= 0.0233 (121/5188). AF 95% confidence interval is 0.0199. There are 2 homozygotes in gnomad4. There are 185 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RY14	NM_014879.4	c.902C>T	p.Pro301Leu	missense_variant	3/3	ENST00000309170.8
MED12L	NM_001393769.1	c.2250+19749G>A		intron_variant		ENST00000687756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RY14	ENST00000309170.8	c.902C>T	p.Pro301Leu	missense_variant	3/3	1	NM_014879.4	P1
MED12L	ENST00000687756.1	c.2250+19749G>A		intron_variant			NM_001393769.1	A2

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 285 AN: 152130 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0235

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00433 AC: 1087 AN: 251024 Hom.: 16 AF XY: 0.00492 AC XY: 668 AN XY: 135718

Gnomad AFR exome AF: 0.000309

Gnomad AMR exome AF: 0.000925

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.0256

Gnomad SAS exome AF: 0.0173

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00183 AC: 2671 AN: 1461734 Hom.: 38 Cov.: 32 AF XY: 0.00228 AC XY: 1655 AN XY: 727164

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000872

Gnomad4 ASJ exome AF: 0.00134

Gnomad4 EAS exome AF: 0.0227

Gnomad4 SAS exome AF: 0.0164

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000110

Gnomad4 OTH exome AF: 0.00245

GnomAD4 genome AF: 0.00186 AC: 283 AN: 152248 Hom.: 2 Cov.: 32 AF XY: 0.00249 AC XY: 185 AN XY: 74438

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.0233

Gnomad4 SAS AF: 0.0193

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00135 Hom.: 3

Bravo AF: 0.00159

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00435 AC: 528

Asia WGS AF: 0.0180 AC: 61 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.39
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.93	D
MetaRNN	Benign	0.013	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.19
Sift	Benign	0.066	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.98	D;D
Vest4		0.20
MVP		0.55
MPC		0.063
ClinPred		0.037	T
GERP RS		4.5
Varity_R		0.29
gMVP		0.46

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: rs74811185; hg19: chr3-150931203;