Variant chr11-66070587-CGCA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_018026.4(PACS1):c.119_121delAGC(p.Gln40del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000558 in 1,478,732 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 0 hom. )

Consequence

PACS1
NM_018026.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.163

Variant links:

Genes affected

PACS1 (HGNC:30032): (phosphofurin acidic cluster sorting protein 1) This gene encodes a protein with a putative role in the localization of trans-Golgi network (TGN) membrane proteins. Mouse and rat homologs have been identified and studies of the homologous rat protein indicate a role in directing TGN localization of furin by binding to the protease's phosphorylated cytosolic domain. In addition, the human protein plays a role in HIV-1 Nef-mediated downregulation of cell surface MHC-I molecules to the TGN, thereby enabling HIV-1 to escape immune surveillance. [provided by RefSeq, Jul 2008]

PACS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 11-66070587-CGCA-C is Benign according to our data. Variant chr11-66070587-CGCA-C is described in ClinVar as [Likely_benign]. Clinvar id is 3060801.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PACS1	NM_018026.4 link	c.119_121delAGC	p.Gln40del	disruptive_inframe_deletion	Exon 1 of 24	ENST00000320580.9	NP_060496.2	Q6VY07-1A0A024R5H6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PACS1	ENST00000320580.9 link	c.119_121delAGC	p.Gln40del	disruptive_inframe_deletion	Exon 1 of 24	1	NM_018026.4	ENSP00000316454.4		Q6VY07-1
PACS1	ENST00000527224.1 link	n.243_245delAGC		non_coding_transcript_exon_variant	Exon 1 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.0000793

AC:

AN:

151372

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00145

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000963

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000591

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000613

AC:

813

AN:

1327254

Hom.:

AF XY:

0.000636

AC XY:

417

AN XY:

655152

show subpopulations

Gnomad4 AFR exome

AF:

0.000483

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.00251

Gnomad4 EAS exome

AF:

0.00117

Gnomad4 SAS exome

AF:

0.000832

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.000505

Gnomad4 OTH exome

AF:

0.000635

GnomAD4 genome

AF:

0.0000792

AC:

AN:

151478

Hom.:

Cov.:

AF XY:

0.0000946

AC XY:

AN XY:

74010

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00145

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000963

Gnomad4 NFE

AF:

0.0000591

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PACS1-related disorder

Benign:1

Mar 14, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over