dbSNP rs5939: PTAFR:p.Asn338Ser (chr1-28150009-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000952.5(PTAFR):c.1013A>G(p.Asn338Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 1,612,284 control chromosomes in the GnomAD database, including 230 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N338D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.022 ( 115 hom., cov: 31)

Exomes 𝑓: 0.0025 ( 115 hom. )

Consequence

PTAFR
NM_000952.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.351

Publications

15 publications found

Variant links:

Genes affected

PTAFR (HGNC:9582): (platelet activating factor receptor) This gene encodes a seven-transmembrane G-protein-coupled receptor for platelet-activating factor (PAF) that localizes to lipid rafts and/or caveolae in the cell membrane. PAF (1-0-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) is a phospholipid that plays a significant role in oncogenic transformation, tumor growth, angiogenesis, metastasis, and pro-inflammatory processes. Binding of PAF to the PAF-receptor (PAFR) stimulates numerous signal transduction pathways including phospholipase C, D, A2, mitogen-activated protein kinases (MAPKs), and the phosphatidylinositol-calcium second messenger system. Following PAFR activation, cells become rapidly desensitized and this refractory state is dependent on PAFR phosphorylation, internalization, and down-regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

PTAFR 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=0.002279222).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PTAFR	NM_000952.5 link	c.1013A>G	p.Asn338Ser	missense_variant	Exon 2 of 2	ENST00000373857.8	NP_000943.1
PTAFR	NM_001164721.2 link	c.1013A>G	p.Asn338Ser	missense_variant	Exon 3 of 3		NP_001158193.1
PTAFR	NM_001164722.3 link	c.1013A>G	p.Asn338Ser	missense_variant	Exon 2 of 2		NP_001158194.1
PTAFR	NM_001164723.3 link	c.1013A>G	p.Asn338Ser	missense_variant	Exon 3 of 3		NP_001158195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PTAFR	ENST00000373857.8 link	c.1013A>G	p.Asn338Ser	missense_variant	Exon 2 of 2	1	NM_000952.5	ENSP00000362965.3
PTAFR	ENST00000305392.3 link	c.1013A>G	p.Asn338Ser	missense_variant	Exon 2 of 2	1		ENSP00000301974.3
PTAFR	ENST00000539896.1 link	c.1013A>G	p.Asn338Ser	missense_variant	Exon 3 of 3	2		ENSP00000442658.1

Frequencies

GnomAD3 genomes

AF:

0.0215

AC:

3274

AN:

152074

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0733

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0202

GnomAD2 exomes

AF:

0.00615

AC:

1538

AN:

250060

AF XY:

0.00469

show subpopulations

Gnomad AFR exome

AF:

0.0794

Gnomad AMR exome

AF:

0.00482

Gnomad ASJ exome

AF:

0.000302

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000505

Gnomad OTH exome

AF:

0.00328

GnomAD4 exome

AF:

0.00254

AC:

3714

AN:

1460092

Hom.:

115

Cov.:

AF XY:

0.00222

AC XY:

1614

AN XY:

726178

show subpopulations

African (AFR)

AF:

0.0747

AC:

2499

AN:

33438

American (AMR)

AF:

0.00558

AC:

249

AN:

44618

Ashkenazi Jewish (ASJ)

AF:

0.000231

AC:

AN:

26028

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.000105

AC:

AN:

86108

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00678

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.000530

AC:

589

AN:

1110764

Other (OTH)

AF:

0.00535

AC:

323

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

207

414

622

829

1036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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:

0.0216

AC:

3286

AN:

152192

Hom.:

115

Cov.:

AF XY:

0.0207

AC XY:

1539

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0734

AC:

3049

AN:

41518

American (AMR)

AF:

0.0107

AC:

164

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000416

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

68010

Other (OTH)

AF:

0.0199

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

148

296

444

592

740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.00796

Hom.:

Bravo

AF:

0.0247

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0735

AC:

324

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00741

AC:

899

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.00113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.028

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.044

T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.24

.;T;.

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N;N

PhyloP100

-0.35

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.090

N;N;N

REVEL

Benign

0.060

Sift

Benign

0.72

T;T;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.059

MVP

0.53

MPC

0.38

ClinPred

0.00016

GERP RS

-1.5

Varity_R

0.021

gMVP

0.13

Mutation Taster

=100/0

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