dbSNP rs1466684: P2RY13:p.Thr179Met (chr3-151328520-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.87 ( 58239 hom., cov: 31)

Exomes 𝑓: 0.84 ( 514957 hom. )

Consequence

P2RY13
NM_176894.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.04

Publications

43 publications found

Variant links:

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]

P2RY13 links:

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

MED12L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
P2RY13	NM_176894.3 link	c.536C>T	p.Thr179Met	missense_variant	Exon 2 of 2	ENST00000325602.6	NP_795713.2
MED12L	NM_001393769.1 link	c.2251-21539G>A		intron_variant	Intron 16 of 44	ENST00000687756.1	NP_001380698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P2RY13	ENST00000325602.6 link	c.536C>T	p.Thr179Met	missense_variant	Exon 2 of 2	1	NM_176894.3	ENSP00000320376.5
MED12L	ENST00000687756.1 link	c.2251-21539G>A		intron_variant	Intron 16 of 44		NM_001393769.1	ENSP00000508695.1

Frequencies

GnomAD3 genomes

AF:

0.873

AC:

132777

AN:

152036

Hom.:

58189

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.861

AC:

215710

AN:

250402

AF XY:

0.862

show subpopulations

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 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.:

AF XY:

0.841

AC XY:

611491

AN XY:

726984

show subpopulations

African (AFR)

AF:

0.959

AC:

32083

AN:

33472

American (AMR)

AF:

0.889

AC:

39704

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.881

AC:

23022

AN:

26136

East Asian (EAS)

AF:

0.839

AC:

33284

AN:

39694

South Asian (SAS)

AF:

0.900

AC:

77611

AN:

86254

European-Finnish (FIN)

AF:

0.839

AC:

44802

AN:

53406

Middle Eastern (MID)

AF:

0.950

AC:

5477

AN:

5768

European-Non Finnish (NFE)

AF:

0.826

AC:

917876

AN:

1111562

Other (OTH)

AF:

0.856

AC:

51656

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

10920

21840

32760

43680

54600

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20994

41988

62982

83976

104970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.873

AC:

132889

AN:

152154

Hom.:

58239

Cov.:

AF XY:

0.875

AC XY:

65050

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.952

AC:

39521

AN:

41510

American (AMR)

AF:

0.875

AC:

13365

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.878

AC:

3048

AN:

3472

East Asian (EAS)

AF:

0.848

AC:

4386

AN:

5170

South Asian (SAS)

AF:

0.901

AC:

4344

AN:

4820

European-Finnish (FIN)

AF:

0.842

AC:

8912

AN:

10586

Middle Eastern (MID)

AF:

0.952

AC:

280

AN:

294

European-Non Finnish (NFE)

AF:

0.830

AC:

56469

AN:

68000

Other (OTH)

AF:

0.893

AC:

1886

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

846

1692

2539

3385

4231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.847

Hom.:

234699

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

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.036

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.11

MetaRNN

Benign

6.2e-7

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-3.2

PhyloP100

5.0

PrimateAI

Benign

0.29

PROVEAN

Benign

3.2

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

0.96

Polyphen

0.0010

Vest4

0.035

MPC

0.10

ClinPred

0.0062

GERP RS

4.3

Varity_R

0.021

gMVP

0.42

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over