2-223734458-G-T

Variant names:

• chr2-223734458-G-T
• rs655783
• ENST00000699384.1:n.909+4695C>A

Variant summary

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

The ENST00000699384.1(AP1S3):​n.909+4695C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,060 control chromosomes in the GnomAD database, including 26,419 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 0.58 (26419 hom., cov: 32)
• Consequence: AP1S3 ENST00000699384.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP1S3	ENST00000699384.1	n.909+4695C>A		intron_variant	Intron 8 of 10
AP1S3	ENST00000699385.1	n.*526+7087C>A		intron_variant	Intron 7 of 7			ENSP00000514349.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88393 AN: 151942 Hom.: 26403 Cov.: 32

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.582 AC: 88450 AN: 152060 Hom.: 26419 Cov.: 32 AF XY: 0.589 AC XY: 43752 AN XY: 74318

African (AFR) AF: 0.708 AC: 29380 AN: 41490

American (AMR) AF: 0.546 AC: 8341 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1554 AN: 3472

East Asian (EAS) AF: 0.543 AC: 2803 AN: 5158

South Asian (SAS) AF: 0.695 AC: 3349 AN: 4822

European-Finnish (FIN) AF: 0.627 AC: 6619 AN: 10560

Middle Eastern (MID) AF: 0.500 AC: 144 AN: 288

European-Non Finnish (NFE) AF: 0.508 AC: 34521 AN: 67970

Other (OTH) AF: 0.536 AC: 1129 AN: 2106

Alfa AF: 0.526 Hom.: 67680

Bravo AF: 0.579

Asia WGS AF: 0.595 AC: 2067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.85
DANN	Benign	0.66
PhyloP100		-0.63

Splicing

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

Other links and lift over

dbSNP: rs655783; hg19: chr2-224599175;