8-80984101-T-C

Variant names:

• chr8-80984101-T-C
• rs999450
• NM_018440.4:c.876+675A>G

Variant summary

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

The NM_018440.4(PAG1):​c.876+675A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,068 control chromosomes in the GnomAD database, including 10,936 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 0.27 (10936 hom., cov: 32)
• Consequence: PAG1 NM_018440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• Publications: 7 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAG1	NM_018440.4	c.876+675A>G		intron_variant	Intron 7 of 8	ENST00000220597.4	NP_060910.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAG1	ENST00000220597.4	c.876+675A>G		intron_variant	Intron 7 of 8	2	NM_018440.4	ENSP00000220597.3

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40767 AN: 151950 Hom.: 10902 Cov.: 32

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.0938

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.269 AC: 40852 AN: 152068 Hom.: 10936 Cov.: 32 AF XY: 0.265 AC XY: 19742 AN XY: 74396

African (AFR) AF: 0.694 AC: 28710 AN: 41386

American (AMR) AF: 0.153 AC: 2339 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 598 AN: 3464

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5186

South Asian (SAS) AF: 0.167 AC: 807 AN: 4826

European-Finnish (FIN) AF: 0.123 AC: 1303 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0937 AC: 6372 AN: 67996

Other (OTH) AF: 0.256 AC: 541 AN: 2116

Alfa AF: 0.286 Hom.: 7533

Bravo AF: 0.290

Asia WGS AF: 0.112 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.76
PhyloP100		-0.62
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: rs999450; hg19: chr8-81896336;