NM_018026.4:c.110_121delAGCAGCAGCAGC

Variant names:

• chr11-66070587-CGCAGCAGCAGCA-C
• rs749515977
• NM_018026.4:c.110_121delAGCAGCAGCAGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_018026.4(PACS1):​c.110_121delAGCAGCAGCAGC​(p.Gln37_Gln40del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000223 in 1,342,472 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: PACS1 NM_018026.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.79
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Schuurs-Hoeijmakers syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet, ClinGen

ENSG00000255038 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_018026.4

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018026.4. 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
	PACS1	NM_018026.4	MANE Select	c.110_121delAGCAGCAGCAGC	p.Gln37_Gln40del	disruptive_inframe_deletion	Exon 1 of 24	NP_060496.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PACS1	ENST00000320580.9	TSL:1 MANE Select	c.110_121delAGCAGCAGCAGC	p.Gln37_Gln40del	disruptive_inframe_deletion	Exon 1 of 24	ENSP00000316454.4	Q6VY07-1
	PACS1	ENST00000527224.1	TSL:2	n.234_245delAGCAGCAGCAGC		non_coding_transcript_exon	Exon 1 of 7
	ENSG00000255038	ENST00000830157.1		n.29+431_29+442delTGCTGCTGCTGC		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000223 AC: 3 AN: 1342472 Hom.: 0 AF XY: 0.00000151 AC XY: 1 AN XY: 663130

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27154

American (AMR) AF: 0.00 AC: 0 AN: 31652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23566

East Asian (EAS) AF: 0.00 AC: 0 AN: 30078

South Asian (SAS) AF: 0.0000398 AC: 3 AN: 75288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4270

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1060426

Other (OTH) AF: 0.00 AC: 0 AN: 55862

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00194278), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs749515977; hg19: chr11-65838058;