2-223765159-C-CCAT

Variant names:

• chr2-223765159-C-CCAT
• rs10644138
• NM_001039569.2:c.429+51_429+53dupATG

Variant summary

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

The NM_001039569.2(AP1S3):​c.429+51_429+53dupATG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 1,529,558 control chromosomes in the GnomAD database, including 16,098 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (6552 hom., cov: 0)
  • Exomes 𝑓: 0.080 (9546 hom.)
• Consequence: AP1S3 NM_001039569.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.488
• 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 -10 ACMG points.

• BP6: Variant 2-223765159-C-CCAT is Benign according to our data. Variant chr2-223765159-C-CCAT is described in ClinVar as Benign. ClinVar VariationId is 2628211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 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.429+51_429+53dupATG		intron	N/A	NP_001034658.1	Q96PC3-4
	AP1S3	NR_110905.2		n.600+51_600+53dupATG		intron	N/A
	AP1S3	NR_110906.2		n.452+51_452+53dupATG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1S3	ENST00000396654.7	TSL:2 MANE Select	c.429+51_429+53dupATG		intron	N/A	ENSP00000379891.2	Q96PC3-4
	AP1S3	ENST00000443700.5	TSL:1	c.429+51_429+53dupATG		intron	N/A	ENSP00000397155.1	Q96PC3-2
	AP1S3	ENST00000415298.5	TSL:1	n.*153+51_*153+53dupATG		intron	N/A	ENSP00000401705.1	Q96PC3-3

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32544 AN: 150776 Hom.: 6536 Cov.: 0

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0483

Gnomad OTH AF: 0.174

GnomAD2 exomes AF: 0.129 AC: 25962 AN: 201824 AF XY: 0.117

Gnomad AFR exome AF: 0.473

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.0664

Gnomad EAS exome AF: 0.344

Gnomad FIN exome AF: 0.0983

Gnomad NFE exome AF: 0.0448

Gnomad OTH exome AF: 0.0893

GnomAD4 exome AF: 0.0801 AC: 110442 AN: 1378662 Hom.: 9546 Cov.: 32 AF XY: 0.0804 AC XY: 55119 AN XY: 685164

African (AFR) AF: 0.501 AC: 15267 AN: 30474

American (AMR) AF: 0.251 AC: 9586 AN: 38240

Ashkenazi Jewish (ASJ) AF: 0.0733 AC: 1754 AN: 23918

East Asian (EAS) AF: 0.369 AC: 14194 AN: 38466

South Asian (SAS) AF: 0.147 AC: 11128 AN: 75944

European-Finnish (FIN) AF: 0.104 AC: 5233 AN: 50414

Middle Eastern (MID) AF: 0.0919 AC: 502 AN: 5460

European-Non Finnish (NFE) AF: 0.0436 AC: 46172 AN: 1058662

Other (OTH) AF: 0.116 AC: 6606 AN: 57084

GnomAD4 genome AF: 0.216 AC: 32602 AN: 150896 Hom.: 6552 Cov.: 0 AF XY: 0.220 AC XY: 16202 AN XY: 73678

African (AFR) AF: 0.514 AC: 21124 AN: 41058

American (AMR) AF: 0.223 AC: 3365 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 248 AN: 3458

East Asian (EAS) AF: 0.411 AC: 2105 AN: 5122

South Asian (SAS) AF: 0.162 AC: 768 AN: 4736

European-Finnish (FIN) AF: 0.114 AC: 1188 AN: 10454

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0483 AC: 3269 AN: 67658

Other (OTH) AF: 0.172 AC: 361 AN: 2100

Alfa AF: 0.0678 Hom.: 1441

ClinVar

ClinVar submissions

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		-0.49
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: rs10644138; hg19: chr2-224629876; COSMIC: COSV104636056; COSMIC: COSV104636056;