rs564343

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-66127695-A-C
• chr11-66127695-A-G
• chr11-66127695-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018026.4(PACS1):​c.356+56853A>C 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: PACS1 NM_018026.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PACS1	NM_018026.4	c.356+56853A>C		intron_variant	Intron 1 of 23	ENST00000320580.9	NP_060496.2
PACS1	XM_011545162.2	c.62+26821A>C		intron_variant	Intron 1 of 23		XP_011543464.2
PACS1	XM_011545164.3	c.17+43465A>C		intron_variant	Intron 1 of 23		XP_011543466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PACS1	ENST00000320580.9	c.356+56853A>C		intron_variant	Intron 1 of 23	1	NM_018026.4	ENSP00000316454.4
PACS1	ENST00000527380.1	c.62+26821A>C		intron_variant	Intron 1 of 4	4		ENSP00000432639.1
PACS1	ENST00000533756.5	c.47+6628A>C		intron_variant	Intron 2 of 4	4		ENSP00000437150.1
PACS1	ENST00000527224.1	n.480+56853A>C		intron_variant	Intron 1 of 6	2

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.052
DANN	Benign	0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65895166;