rs1466684

chr3-151328520-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176894.3(P2RY13):c.536C>T(p.Thr179Met) variant causes a missense change. The variant allele was found at a frequency of 0.842 in 1,613,500 control chromosomes in the GnomAD database, including 573,196 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.87 (58239 hom., cov: 31)
  • Exomes 𝑓: 0.84 (514957 hom.)
• Consequence: P2RY13 NM_176894.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.04

Genes affected

P2RY13 (HGNC:4537): (purinergic receptor P2Y13) The product of this gene belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is activated by ADP. [provided by RefSeq, Sep 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.1681396E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P2RY13	NM_176894.3	c.536C>T	p.Thr179Met	missense_variant	2/2	ENST00000325602.6
MED12L	NM_001393769.1	c.2251-21539G>A		intron_variant		ENST00000687756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P2RY13	ENST00000325602.6	c.536C>T	p.Thr179Met	missense_variant	2/2	1	NM_176894.3	P1
MED12L	ENST00000687756.1	c.2251-21539G>A		intron_variant			NM_001393769.1	A2

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132777 AN: 152036 Hom.: 58189 Cov.: 31

Gnomad AFR AF: 0.952

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.902

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.897

GnomAD3 exomes AF: 0.861 AC: 215710 AN: 250402 Hom.: 93136 AF XY: 0.862 AC XY: 116676 AN XY: 135394

Gnomad AFR exome AF: 0.953

Gnomad AMR exome AF: 0.889

Gnomad ASJ exome AF: 0.883

Gnomad EAS exome AF: 0.843

Gnomad SAS exome AF: 0.902

Gnomad FIN exome AF: 0.841

Gnomad NFE exome AF: 0.834

Gnomad OTH exome AF: 0.855

GnomAD4 exome AF: 0.839 AC: 1225515 AN: 1461346 Hom.: 514957 Cov.: 50 AF XY: 0.841 AC XY: 611491 AN XY: 726984

Gnomad4 AFR exome AF: 0.959

Gnomad4 AMR exome AF: 0.889

Gnomad4 ASJ exome AF: 0.881

Gnomad4 EAS exome AF: 0.839

Gnomad4 SAS exome AF: 0.900

Gnomad4 FIN exome AF: 0.839

Gnomad4 NFE exome AF: 0.826

Gnomad4 OTH exome AF: 0.856

GnomAD4 genome AF: 0.873 AC: 132889 AN: 152154 Hom.: 58239 Cov.: 31 AF XY: 0.875 AC XY: 65050 AN XY: 74376

Gnomad4 AFR AF: 0.952

Gnomad4 AMR AF: 0.875

Gnomad4 ASJ AF: 0.878

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.901

Gnomad4 FIN AF: 0.842

Gnomad4 NFE AF: 0.830

Gnomad4 OTH AF: 0.893

Alfa AF: 0.844 Hom.: 133651

Bravo AF: 0.880

TwinsUK AF: 0.823 AC: 3050

ALSPAC AF: 0.814 AC: 3136

ESP6500AA AF: 0.948 AC: 4175

ESP6500EA AF: 0.833 AC: 7160

ExAC AF: 0.863 AC: 104815

Asia WGS AF: 0.845 AC: 2941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	14
Dann	Benign	0.71
DEOGEN2	Benign	0.036	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.11	T
MetaRNN	Benign	6.2e-7	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-3.2	N
MutationTaster	Benign	1.5e-14	P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	3.2	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	0.96	T
Polyphen		0.0010	B
Vest4		0.035
MPC		0.10
ClinPred		0.0062	T
GERP RS		4.3
Varity_R		0.021
gMVP		0.42

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: rs1466684; hg19: chr3-151046308; COSMIC: COSV56380424;