3-151340653-A-G

Variant names:

• chr3-151340653-A-G
• rs3821667
• NM_022788.5:c.-72T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022788.5(P2RY12):​c.-72T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 152,618 control chromosomes in the GnomAD database, including 54,992 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.85 (54843 hom., cov: 33)
  • Exomes 𝑓: 0.83 (149 hom.)
• Consequence: P2RY12 NM_022788.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 7 publications found

Genes affected

P2RY12 (HGNC:18124): (purinergic receptor P2Y12) 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 involved in platelet aggregation, and is a potential target for the treatment of thromboembolisms and other clotting disorders. Mutations in this gene are implicated in bleeding disorder, platelet type 8 (BDPLT8). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
P2RY12	NM_022788.5	c.-72T>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 3	ENST00000302632.4	NP_073625.1
P2RY12	NM_022788.5	c.-72T>C		5_prime_UTR_variant	Exon 2 of 3	ENST00000302632.4	NP_073625.1
MED12L	NM_001393769.1	c.2251-9406A>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
P2RY12	ENST00000302632.4	c.-72T>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 3	1	NM_022788.5	ENSP00000307259.4
P2RY12	ENST00000302632.4	c.-72T>C		5_prime_UTR_variant	Exon 2 of 3	1	NM_022788.5	ENSP00000307259.4
MED12L	ENST00000687756.1	c.2251-9406A>G		intron_variant	Intron 16 of 44		NM_001393769.1	ENSP00000508695.1

Frequencies

GnomAD3 genomes AF: 0.849 AC: 129068 AN: 152064 Hom.: 54813 Cov.: 33

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.880

GnomAD4 exome AF: 0.828 AC: 361 AN: 436 Hom.: 149 Cov.: 0 AF XY: 0.837 AC XY: 221 AN XY: 264

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.826 AC: 352 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.849 AC: 129152 AN: 152182 Hom.: 54843 Cov.: 33 AF XY: 0.851 AC XY: 63317 AN XY: 74402

African (AFR) AF: 0.862 AC: 35792 AN: 41536

American (AMR) AF: 0.867 AC: 13247 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3051 AN: 3472

East Asian (EAS) AF: 0.850 AC: 4392 AN: 5170

South Asian (SAS) AF: 0.900 AC: 4343 AN: 4826

European-Finnish (FIN) AF: 0.842 AC: 8927 AN: 10602

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56583 AN: 67984

Other (OTH) AF: 0.875 AC: 1849 AN: 2114

Alfa AF: 0.846 Hom.: 70029

Bravo AF: 0.850

Asia WGS AF: 0.837 AC: 2910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.10
DANN	Benign	0.63
PhyloP100		-1.1
Mutation Taster		=300/0	polymorphism (auto)

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: rs3821667; hg19: chr3-151058441; COSMIC: COSV56381334; COSMIC: COSV56381334;