8-80980674-G-T

Variant names:

• chr8-80980674-G-T
• rs6984368
• NM_018440.4:c.877-180C>A

Variant summary

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

The NM_018440.4(PAG1):​c.877-180C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,056 control chromosomes in the GnomAD database, including 6,137 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 0.23 (6137 hom., cov: 32)
• Consequence: PAG1 NM_018440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 6 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018440.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAG1	NM_018440.4	MANE Select	c.877-180C>A		intron	N/A	NP_060910.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAG1	ENST00000220597.4	TSL:2 MANE Select	c.877-180C>A		intron	N/A	ENSP00000220597.3
	PAG1	ENST00000970332.1		c.1033-180C>A		intron	N/A	ENSP00000640391.1
	PAG1	ENST00000970333.1		c.1033-180C>A		intron	N/A	ENSP00000640392.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34558 AN: 151938 Hom.: 6122 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.232

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.228 AC: 34615 AN: 152056 Hom.: 6137 Cov.: 32 AF XY: 0.226 AC XY: 16774 AN XY: 74332

African (AFR) AF: 0.494 AC: 20460 AN: 41426

American (AMR) AF: 0.145 AC: 2223 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 634 AN: 3466

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5190

South Asian (SAS) AF: 0.176 AC: 849 AN: 4818

European-Finnish (FIN) AF: 0.172 AC: 1818 AN: 10572

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7916 AN: 67980

Other (OTH) AF: 0.229 AC: 483 AN: 2112

Alfa AF: 0.216 Hom.: 4065

Bravo AF: 0.237

Asia WGS AF: 0.0990 AC: 346 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.32
DANN	Benign	0.48
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs6984368; hg19: chr8-81892909;