dbSNP rs7006101: PAG1:p.Ser229Ser (chr8-80984965-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_018440.4(PAG1):c.687G>A(p.Ser229Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,613,860 control chromosomes in the GnomAD database, including 10,400 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 0.14 ( 1869 hom., cov: 32)

Exomes 𝑓: 0.099 ( 8531 hom. )

Consequence

PAG1
NM_018440.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.88

Publications

13 publications found

Variant links:

Genes affected

PAG1 (HGNC:30043): (phosphoprotein membrane anchor with glycosphingolipid microdomains 1) The protein encoded by this gene is a type III transmembrane adaptor protein that binds to the tyrosine kinase csk protein. It is thought to be involved in the regulation of T cell activation. [provided by RefSeq, Jul 2008]

PAG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP7

Synonymous conserved (PhyloP=-3.88 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAG1	NM_018440.4 link	c.687G>A	p.Ser229Ser	synonymous_variant	Exon 7 of 9	ENST00000220597.4	NP_060910.3	Q9NWQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAG1	ENST00000220597.4 link	c.687G>A	p.Ser229Ser	synonymous_variant	Exon 7 of 9	2	NM_018440.4	ENSP00000220597.3		Q9NWQ8

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21124

AN:

151962

Hom.:

1866

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.0921

Gnomad OTH

AF:

0.156

GnomAD2 exomes

AF:

0.111

AC:

28025

AN:

251422

AF XY:

0.115

show subpopulations

Gnomad AFR exome

AF:

0.256

Gnomad AMR exome

AF:

0.0703

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.000816

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.0989

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.0990

AC:

144716

AN:

1461780

Hom.:

8531

Cov.:

AF XY:

0.102

AC XY:

74035

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.253

AC:

8466

AN:

33478

American (AMR)

AF:

0.0758

AC:

3392

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

4139

AN:

26136

East Asian (EAS)

AF:

0.000554

AC:

AN:

39700

South Asian (SAS)

AF:

0.177

AC:

15228

AN:

86258

European-Finnish (FIN)

AF:

0.113

AC:

6062

AN:

53420

Middle Eastern (MID)

AF:

0.230

AC:

1326

AN:

5766

European-Non Finnish (NFE)

AF:

0.0891

AC:

99032

AN:

1111902

Other (OTH)

AF:

0.117

AC:

7049

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

7663

15326

22990

30653

38316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3696

7392

11088

14784

18480

<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:

0.139

AC:

21154

AN:

152080

Hom.:

1869

Cov.:

AF XY:

0.140

AC XY:

10426

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.245

AC:

10174

AN:

41454

American (AMR)

AF:

0.104

AC:

1591

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

543

AN:

3468

East Asian (EAS)

AF:

0.00212

AC:

AN:

5184

South Asian (SAS)

AF:

0.165

AC:

796

AN:

4818

European-Finnish (FIN)

AF:

0.122

AC:

1295

AN:

10588

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0920

AC:

6256

AN:

67990

Other (OTH)

AF:

0.153

AC:

324

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

893

1786

2680

3573

4466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.115

Hom.:

1221

Bravo

AF:

0.143

Asia WGS

AF:

0.0780

AC:

272

AN:

3478

EpiCase

AF:

0.107

EpiControl

AF:

0.104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.22

(source)

DANN

Benign

0.73

PhyloP100

-3.9

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