chr11-66070648-C-T

Variant names:

• chr11-66070648-C-T
• rs1209337870
• NM_018026.4:c.162C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_018026.4(PACS1):​c.162C>T​(p.Thr54Thr) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. T54T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PACS1 NM_018026.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325
• 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: G2P, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000255038 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.325 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PACS1	NM_018026.4	c.162C>T	p.Thr54Thr	synonymous_variant	Exon 1 of 24	ENST00000320580.9	NP_060496.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PACS1	ENST00000320580.9	c.162C>T	p.Thr54Thr	synonymous_variant	Exon 1 of 24	1	NM_018026.4	ENSP00000316454.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 186946 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1409530 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 701156

African (AFR) AF: 0.00 AC: 0 AN: 29814

American (AMR) AF: 0.00 AC: 0 AN: 42004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25056

East Asian (EAS) AF: 0.00 AC: 0 AN: 35810

South Asian (SAS) AF: 0.00 AC: 0 AN: 82154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5464

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092066

Other (OTH) AF: 0.00 AC: 0 AN: 58588

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		0.33
PromoterAI		0.029	Neutral

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: rs1209337870; hg19: chr11-65838119;