chr11-66070587-CGCA-C

Position:

• chr11-66070587-CGCA-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_018026.4(PACS1):​c.119_121del​(p.Gln40del) variant causes a 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). Synonymous variant affecting the same amino acid position (i.e. P34P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00061 (0 hom.)
• Consequence: PACS1 NM_018026.4 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.163

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]

ACMG classification

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/exons	MANE	UniProt
PACS1	NM_018026.4	c.119_121del	p.Gln40del	inframe_deletion	1/24	ENST00000320580.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PACS1	ENST00000320580.9	c.119_121del	p.Gln40del	inframe_deletion	1/24	1	NM_018026.4	P2
PACS1	ENST00000527224.1	n.243_245del		non_coding_transcript_exon_variant	1/7	2

Frequencies

GnomAD3 genomes AF: 0.0000793 AC: 12 AN: 151372 Hom.: 0 Cov.: 32

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.: 0 AF XY: 0.000636 AC XY: 417 AN XY: 655152

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: 12 AN: 151478 Hom.: 0 Cov.: 32 AF XY: 0.0000946 AC XY: 7 AN XY: 74010

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: criteria provided, single submitter

Submissions by phenotype

PACS1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 14, 2019

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

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: rs749515977; hg19: chr11-65838058;