NM_018026.4:c.356+56853A>G

Variant names:

• chr11-66127695-A-G
• rs564343
• NM_018026.4:c.356+56853A>G

Variant summary

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

The NM_018026.4(PACS1):​c.356+56853A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,122 control chromosomes in the GnomAD database, including 18,091 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 0.47 (18091 hom., cov: 32)
• Consequence: PACS1 NM_018026.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 27 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: G2P, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

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.356+56853A>G		intron	N/A	NP_060496.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PACS1	ENST00000320580.9	TSL:1 MANE Select	c.356+56853A>G		intron	N/A	ENSP00000316454.4
	PACS1	ENST00000527380.1	TSL:4	c.62+26821A>G		intron	N/A	ENSP00000432639.1
	PACS1	ENST00000533756.5	TSL:4	c.47+6628A>G		intron	N/A	ENSP00000437150.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 71035 AN: 152004 Hom.: 18095 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.467 AC: 71040 AN: 152122 Hom.: 18091 Cov.: 32 AF XY: 0.465 AC XY: 34612 AN XY: 74362

African (AFR) AF: 0.272 AC: 11276 AN: 41510

American (AMR) AF: 0.426 AC: 6507 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1961 AN: 3472

East Asian (EAS) AF: 0.321 AC: 1658 AN: 5172

South Asian (SAS) AF: 0.630 AC: 3039 AN: 4820

European-Finnish (FIN) AF: 0.551 AC: 5818 AN: 10558

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38940 AN: 67996

Other (OTH) AF: 0.492 AC: 1038 AN: 2110

Alfa AF: 0.519 Hom.: 33275

Bravo AF: 0.443

Asia WGS AF: 0.463 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.059
DANN	Benign	0.49
PhyloP100		-1.5
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: rs564343; hg19: chr11-65895166;