chr2-223776086-C-CAA

Variant names:

• chr2-223776086-C-CAA
• rs59118867
• NM_001039569.2:c.183-78_183-77insTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001039569.2(AP1S3):​c.183-78_183-77insTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,041,924 control chromosomes in the GnomAD database, including 30,782 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (3938 hom., cov: 25)
  • Exomes 𝑓: 0.24 (26844 hom.)
• Consequence: AP1S3 NM_001039569.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.413
• 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 -10 ACMG points.

• BP6: Variant 2-223776086-C-CAA is Benign according to our data. Variant chr2-223776086-C-CAA is described in ClinVar as Benign. ClinVar VariationId is 2628237.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1S3	NM_001039569.2	MANE Select	c.183-78_183-77insTT		intron	N/A	NP_001034658.1	Q96PC3-4
	AP1S3	NR_110905.2		n.315-78_315-77insTT		intron	N/A
	AP1S3	NR_110906.2		n.314+1604_314+1605insTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1S3	ENST00000396654.7	TSL:2 MANE Select	c.183-78_183-77insTT		intron	N/A	ENSP00000379891.2	Q96PC3-4
	AP1S3	ENST00000443700.5	TSL:1	c.183-78_183-77insTT		intron	N/A	ENSP00000397155.1	Q96PC3-2
	AP1S3	ENST00000446015.6	TSL:1	c.183-78_183-77insTT		intron	N/A	ENSP00000388738.2	Q96PC3-1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34371 AN: 151884 Hom.: 3931 Cov.: 25

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.223

GnomAD2 exomes AF: 0.210 AC: 33479 AN: 159596 AF XY: 0.211

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.234

Gnomad EAS exome AF: 0.179

Gnomad FIN exome AF: 0.202

Gnomad NFE exome AF: 0.252

Gnomad OTH exome AF: 0.217

GnomAD4 exome AF: 0.241 AC: 214269 AN: 889922 Hom.: 26844 Cov.: 12 AF XY: 0.239 AC XY: 110128 AN XY: 459942

African (AFR) AF: 0.228 AC: 4922 AN: 21560

American (AMR) AF: 0.156 AC: 5497 AN: 35258

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 5123 AN: 21980

East Asian (EAS) AF: 0.212 AC: 7073 AN: 33340

South Asian (SAS) AF: 0.170 AC: 11790 AN: 69270

European-Finnish (FIN) AF: 0.202 AC: 9880 AN: 49026

Middle Eastern (MID) AF: 0.219 AC: 1040 AN: 4742

European-Non Finnish (NFE) AF: 0.260 AC: 159225 AN: 613426

Other (OTH) AF: 0.235 AC: 9719 AN: 41320

GnomAD4 genome AF: 0.226 AC: 34416 AN: 152002 Hom.: 3938 Cov.: 25 AF XY: 0.222 AC XY: 16503 AN XY: 74304

African (AFR) AF: 0.221 AC: 9169 AN: 41432

American (AMR) AF: 0.200 AC: 3057 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3472

East Asian (EAS) AF: 0.187 AC: 967 AN: 5168

South Asian (SAS) AF: 0.160 AC: 770 AN: 4822

European-Finnish (FIN) AF: 0.195 AC: 2054 AN: 10554

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.248 AC: 16872 AN: 67964

Other (OTH) AF: 0.224 AC: 473 AN: 2108

Alfa AF: 0.238 Hom.: 784

Bravo AF: 0.227

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs59118867; hg19: chr2-224640803; COSMIC: COSV57509535;