2-223696612-C-T

Variant names:

• chr2-223696612-C-T
• rs734556
• ENST00000699384.1:n.1032-2070G>A

Variant summary

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

The ENST00000699384.1(AP1S3):​n.1032-2070G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 152,078 control chromosomes in the GnomAD database, including 22,191 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 0.48 (22191 hom., cov: 32)
• Consequence: AP1S3 ENST00000699384.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 5 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000699384.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1S3	ENST00000699384.1		n.1032-2070G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73038 AN: 151960 Hom.: 22197 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.480 AC: 73036 AN: 152078 Hom.: 22191 Cov.: 32 AF XY: 0.483 AC XY: 35907 AN XY: 74348

African (AFR) AF: 0.121 AC: 5038 AN: 41508

American (AMR) AF: 0.490 AC: 7486 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1938 AN: 3464

East Asian (EAS) AF: 0.189 AC: 976 AN: 5168

South Asian (SAS) AF: 0.590 AC: 2840 AN: 4810

European-Finnish (FIN) AF: 0.773 AC: 8190 AN: 10596

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44802 AN: 67964

Other (OTH) AF: 0.503 AC: 1055 AN: 2096

Alfa AF: 0.581 Hom.: 53714

Bravo AF: 0.440

Asia WGS AF: 0.398 AC: 1387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.63
DANN	Benign	0.51
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs734556; hg19: chr2-224561329;