rs55944411

Variant names:

• chr2-223776179-T-C
• rs55944411
• NM_001039569.2:c.183-170A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001039569.2(AP1S3):​c.183-170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 701,156 control chromosomes in the GnomAD database, including 6,494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (3001 hom., cov: 32)
  • Exomes 𝑓: 0.088 (3493 hom.)
• Consequence: AP1S3 NM_001039569.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.45
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-223776179-T-C is Benign according to our data. Variant chr2-223776179-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688467.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 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.183-170A>G		intron	N/A	NP_001034658.1	Q96PC3-4
	AP1S3	NR_110905.2		n.315-170A>G		intron	N/A
	AP1S3	NR_110906.2		n.314+1512A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1S3	ENST00000396654.7	TSL:2 MANE Select	c.183-170A>G		intron	N/A	ENSP00000379891.2	Q96PC3-4
	AP1S3	ENST00000443700.5	TSL:1	c.183-170A>G		intron	N/A	ENSP00000397155.1	Q96PC3-2
	AP1S3	ENST00000446015.6	TSL:1	c.183-170A>G		intron	N/A	ENSP00000388738.2	Q96PC3-1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23171 AN: 152050 Hom.: 2997 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0939

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0870

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0465

Gnomad OTH AF: 0.133

GnomAD2 exomes AF: 0.118 AC: 17738 AN: 150432 AF XY: 0.114

Gnomad AFR exome AF: 0.360

Gnomad AMR exome AF: 0.163

Gnomad ASJ exome AF: 0.0924

Gnomad EAS exome AF: 0.276

Gnomad FIN exome AF: 0.0821

Gnomad NFE exome AF: 0.0451

Gnomad OTH exome AF: 0.0880

GnomAD4 exome AF: 0.0876 AC: 48105 AN: 548988 Hom.: 3493 Cov.: 5 AF XY: 0.0885 AC XY: 26225 AN XY: 296250

African (AFR) AF: 0.340 AC: 5250 AN: 15460

American (AMR) AF: 0.159 AC: 5408 AN: 34020

Ashkenazi Jewish (ASJ) AF: 0.0932 AC: 1813 AN: 19460

East Asian (EAS) AF: 0.199 AC: 6147 AN: 30838

South Asian (SAS) AF: 0.139 AC: 8580 AN: 61524

European-Finnish (FIN) AF: 0.0795 AC: 3670 AN: 46152

Middle Eastern (MID) AF: 0.0836 AC: 332 AN: 3970

European-Non Finnish (NFE) AF: 0.0456 AC: 14049 AN: 307954

Other (OTH) AF: 0.0965 AC: 2856 AN: 29610

GnomAD4 genome AF: 0.152 AC: 23201 AN: 152168 Hom.: 3001 Cov.: 32 AF XY: 0.155 AC XY: 11521 AN XY: 74376

African (AFR) AF: 0.344 AC: 14252 AN: 41468

American (AMR) AF: 0.135 AC: 2065 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0939 AC: 326 AN: 3472

East Asian (EAS) AF: 0.253 AC: 1313 AN: 5182

South Asian (SAS) AF: 0.151 AC: 726 AN: 4822

European-Finnish (FIN) AF: 0.0870 AC: 921 AN: 10586

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0465 AC: 3165 AN: 68028

Other (OTH) AF: 0.131 AC: 276 AN: 2112

Alfa AF: 0.0971 Hom.: 583

Bravo AF: 0.167

Asia WGS AF: 0.230 AC: 804 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
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.22
DANN	Benign	0.48
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs55944411; hg19: chr2-224640896; COSMIC: COSV57510926;