8-80984101-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018440.4(PAG1):​c.876+675A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAG1	NM_018440.4	MANE Select	c.876+675A>T		intron	N/A	NP_060910.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAG1	ENST00000220597.4	TSL:2 MANE Select	c.876+675A>T		intron	N/A	ENSP00000220597.3	Q9NWQ8
	PAG1	ENST00000970332.1		c.1032+675A>T		intron	N/A	ENSP00000640391.1
	PAG1	ENST00000970333.1		c.1032+675A>T		intron	N/A	ENSP00000640392.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 7533

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.2
DANN	Benign	0.77
PhyloP100		-0.62

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;