chr2-223771773-A-C

Variant names:

• chr2-223771773-A-C
• rs7603262
• NM_001039569.2:c.291+4128T>G

Variant summary

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

The NM_001039569.2(AP1S3):​c.291+4128T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,152 control chromosomes in the GnomAD database, including 8,407 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 0.26 (8407 hom., cov: 33)
• Consequence: AP1S3 NM_001039569.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.975
• Publications: 3 publications found

Genes affected

AP1S3 (HGNC:18971): (adaptor related protein complex 1 subunit sigma 3) This gene encodes a member of the adaptor-related protein complex 1, sigma subunit genes. The encoded protein is a component of adaptor protein complex 1 (AP-1), one of the AP complexes involved in claathrin-mediated vesicular transport from the Golgi or endosomes. Disruption of the pathway for display of HIV-1 antigens, which prevents recognition of the virus by cytotoxic T cells, has been shown to involve the AP-1 complex (PMID: 15569716). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

AP1S3 Gene-Disease associations (from GenCC):

• psoriasis 15, pustular, susceptibility to

  Inheritance: AD Classification: STRONG Submitted by: G2P
• pustulosis palmaris et plantaris

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• psoriasis 14, pustular

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286239 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039569.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1S3	NM_001039569.2	MANE Select	c.291+4128T>G		intron	N/A	NP_001034658.1
	AP1S3	NR_110905.2		n.462+1540T>G		intron	N/A
	AP1S3	NR_110906.2		n.314+5918T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1S3	ENST00000396654.7	TSL:2 MANE Select	c.291+4128T>G		intron	N/A	ENSP00000379891.2
	AP1S3	ENST00000443700.5	TSL:1	c.291+4128T>G		intron	N/A	ENSP00000397155.1
	AP1S3	ENST00000446015.6	TSL:1	c.291+4128T>G		intron	N/A	ENSP00000388738.2

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39724 AN: 152034 Hom.: 8382 Cov.: 33

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.0832

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.262 AC: 39803 AN: 152152 Hom.: 8407 Cov.: 33 AF XY: 0.266 AC XY: 19822 AN XY: 74396

African (AFR) AF: 0.542 AC: 22499 AN: 41476

American (AMR) AF: 0.328 AC: 5019 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 449 AN: 3470

East Asian (EAS) AF: 0.581 AC: 3006 AN: 5172

South Asian (SAS) AF: 0.214 AC: 1032 AN: 4830

European-Finnish (FIN) AF: 0.132 AC: 1403 AN: 10602

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.0832 AC: 5655 AN: 68002

Other (OTH) AF: 0.240 AC: 508 AN: 2114

Alfa AF: 0.140 Hom.: 1629

Bravo AF: 0.294

Asia WGS AF: 0.422 AC: 1469 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.0
DANN	Benign	0.75
PhyloP100		0.97
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: rs7603262; hg19: chr2-224636490;