rs1554990856

Positions:

• chr11-66216738-C-G
• chr11-66216738-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_018026.4(PACS1):​c.941C>G​(p.Thr314Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.43

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PACS1. . Gene score misZ 3.71 (greater than the threshold 3.09). Trascript score misZ 3.8723 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, Schuurs-Hoeijmakers syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.06406379).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PACS1	NM_018026.4	c.941C>G	p.Thr314Ser	missense_variant	7/24	ENST00000320580.9	NP_060496.2
PACS1	XM_011545162.2	c.647C>G	p.Thr216Ser	missense_variant	7/24		XP_011543464.2
PACS1	XM_011545164.3	c.602C>G	p.Thr201Ser	missense_variant	7/24		XP_011543466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PACS1	ENST00000320580.9	c.941C>G	p.Thr314Ser	missense_variant	7/24	1	NM_018026.4	ENSP00000316454.4
PACS1	ENST00000524784.1	n.113C>G		non_coding_transcript_exon_variant	2/6	4		ENSP00000435037.1
PACS1	ENST00000527224.1	n.1065C>G		non_coding_transcript_exon_variant	7/7	2
PACS1	ENST00000531298.5	n.200C>G		non_coding_transcript_exon_variant	3/5	4		ENSP00000437274.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.10
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.064
Sift	Benign	0.72	T
Sift4G	Benign	1.0	T
Polyphen		0.020	B
Vest4		0.078
MutPred		0.19		Gain of methylation at K317 (P = 0.1096);
MVP		0.24
MPC		0.70
ClinPred		0.68	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.077
gMVP		0.16

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: rs1554990856; hg19: chr11-65984209;