rs74811185

Variant names:

• chr3-151213415-G-A
• rs74811185
• NM_014879.4:c.902C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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: Ambry Genetics, ClinGen, Illumina, Labcorp Genetics (formerly Invitae)
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.902C>T	p.Pro301Leu	missense	Exon 3 of 3	NP_055694.3
	MED12L	NM_001393769.1	MANE Select	c.2250+19749G>A		intron	N/A	NP_001380698.1	A0A8I5KX78
	P2RY14	NM_001081455.2		c.902C>T	p.Pro301Leu	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.902C>T	p.Pro301Leu	missense	Exon 3 of 3	ENSP00000308361.3	Q15391
	MED12L	ENST00000687756.1	MANE Select	c.2250+19749G>A		intron	N/A	ENSP00000508695.1	A0A8I5KX78
	MED12L	ENST00000474524.5	TSL:1	c.2145+19749G>A		intron	N/A	ENSP00000417235.1	Q86YW9-1

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

GnomAD2 exomes AF: 0.00433 AC: 1087 AN: 251024 AF XY: 0.00492

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 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

African (AFR) AF: 0.000239 AC: 8 AN: 33478

American (AMR) AF: 0.000872 AC: 39 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00134 AC: 35 AN: 26132

East Asian (EAS) AF: 0.0227 AC: 901 AN: 39686

South Asian (SAS) AF: 0.0164 AC: 1412 AN: 86250

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53406

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000110 AC: 122 AN: 1111900

Other (OTH) AF: 0.00245 AC: 148 AN: 60390

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

African (AFR) AF: 0.000193 AC: 8 AN: 41536

American (AMR) AF: 0.00314 AC: 48 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.0233 AC: 121 AN: 5188

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4826

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68008

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.00140 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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.5
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.19
Sift	Benign	0.066	T
Sift4G	Benign	0.52	T
Polyphen		0.98	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
Mutation Taster		=99/1	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: rs74811185; hg19: chr3-150931203;