chr2-223776146-C-T

Variant names:

• chr2-223776146-C-T
• rs11902103
• NM_001039569.2:c.183-137G>A

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.183-137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 718,880 control chromosomes in the GnomAD database, including 6,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2998 hom., cov: 33)
  • Exomes 𝑓: 0.087 (3542 hom.)
• Consequence: AP1S3 NM_001039569.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.306
• Publications: 4 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=-0.84).
• BP6: Variant 2-223776146-C-T is Benign according to our data. Variant chr2-223776146-C-T is described in ClinVar as Benign. ClinVar VariationId is 2628301.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.183-137G>A		intron	N/A	NP_001034658.1	Q96PC3-4
	AP1S3	NR_110905.2		n.315-137G>A		intron	N/A
	AP1S3	NR_110906.2		n.314+1545G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1S3	ENST00000396654.7	TSL:2 MANE Select	c.183-137G>A		intron	N/A	ENSP00000379891.2	Q96PC3-4
	AP1S3	ENST00000443700.5	TSL:1	c.183-137G>A		intron	N/A	ENSP00000397155.1	Q96PC3-2
	AP1S3	ENST00000446015.6	TSL:1	c.183-137G>A		intron	N/A	ENSP00000388738.2	Q96PC3-1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23161 AN: 152040 Hom.: 2994 Cov.: 33

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0939

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0868

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0465

Gnomad OTH AF: 0.133

GnomAD2 exomes AF: 0.117 AC: 18018 AN: 154208 AF XY: 0.112

Gnomad AFR exome AF: 0.360

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.0919

Gnomad EAS exome AF: 0.276

Gnomad FIN exome AF: 0.0818

Gnomad NFE exome AF: 0.0448

Gnomad OTH exome AF: 0.0886

GnomAD4 exome AF: 0.0868 AC: 49175 AN: 566722 Hom.: 3542 Cov.: 5 AF XY: 0.0875 AC XY: 26765 AN XY: 305738

African (AFR) AF: 0.339 AC: 5350 AN: 15792

American (AMR) AF: 0.158 AC: 5453 AN: 34518

Ashkenazi Jewish (ASJ) AF: 0.0924 AC: 1835 AN: 19854

East Asian (EAS) AF: 0.198 AC: 6277 AN: 31726

South Asian (SAS) AF: 0.139 AC: 8612 AN: 62062

European-Finnish (FIN) AF: 0.0790 AC: 3801 AN: 48124

Middle Eastern (MID) AF: 0.0845 AC: 343 AN: 4058

European-Non Finnish (NFE) AF: 0.0455 AC: 14559 AN: 320052

Other (OTH) AF: 0.0964 AC: 2945 AN: 30536

GnomAD4 genome AF: 0.152 AC: 23190 AN: 152158 Hom.: 2998 Cov.: 33 AF XY: 0.155 AC XY: 11513 AN XY: 74388

African (AFR) AF: 0.344 AC: 14251 AN: 41474

American (AMR) AF: 0.135 AC: 2059 AN: 15286

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

East Asian (EAS) AF: 0.254 AC: 1313 AN: 5174

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

European-Finnish (FIN) AF: 0.0868 AC: 921 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0465 AC: 3161 AN: 68014

Other (OTH) AF: 0.131 AC: 276 AN: 2106

Alfa AF: 0.112 Hom.: 585

Bravo AF: 0.167

Asia WGS AF: 0.230 AC: 802 AN: 3478

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
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.44
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs11902103; hg19: chr2-224640863; COSMIC: COSV57510919;