rs7006101

chr8-80984965-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018440.4(PAG1):c.687G>A(p.Ser229=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.88

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PAG1	NM_018440.4	c.687G>A	p.Ser229=	synonymous_variant	7/9	ENST00000220597.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAG1	ENST00000220597.4	c.687G>A	p.Ser229=	synonymous_variant	7/9	2	NM_018440.4	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21124 AN: 151962 Hom.: 1866 Cov.: 32

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

GnomAD3 exomes AF: 0.111 AC: 28025 AN: 251422 Hom.: 2020 AF XY: 0.115 AC XY: 15675 AN XY: 135886

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 SAS exome AF: 0.176

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.: 33 AF XY: 0.102 AC XY: 74035 AN XY: 727202

Gnomad4 AFR exome AF: 0.253

Gnomad4 AMR exome AF: 0.0758

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.000554

Gnomad4 SAS exome AF: 0.177

Gnomad4 FIN exome AF: 0.113

Gnomad4 NFE exome AF: 0.0891

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.139 AC: 21154 AN: 152080 Hom.: 1869 Cov.: 32 AF XY: 0.140 AC XY: 10426 AN XY: 74366

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0920

Gnomad4 OTH AF: 0.153

Alfa AF: 0.114 Hom.: 939

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
Dann	Benign	0.73

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: rs7006101; hg19: chr8-81897200;