2-223765159-C-CCATCAT

Variant names:

• chr2-223765159-C-CCATCAT
• rs10644138
• NM_001039569.2:c.429+48_429+53dupATGATG

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+48_429+53dupATGATG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,558,338 control chromosomes in the GnomAD database, including 146,314 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (12511 hom., cov: 0)
  • Exomes 𝑓: 0.45 (133803 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-CCATCAT is Benign according to our data. Variant chr2-223765159-C-CCATCAT is described in ClinVar as Benign. ClinVar VariationId is 2628169.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.564 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+48_429+53dupATGATG		intron	N/A	NP_001034658.1	Q96PC3-4
	AP1S3	NR_110905.2		n.600+48_600+53dupATGATG		intron	N/A
	AP1S3	NR_110906.2		n.452+48_452+53dupATGATG		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+48_429+53dupATGATG		intron	N/A	ENSP00000379891.2	Q96PC3-4
	AP1S3	ENST00000443700.5	TSL:1	c.429+48_429+53dupATGATG		intron	N/A	ENSP00000397155.1	Q96PC3-2
	AP1S3	ENST00000415298.5	TSL:1	n.*153+48_*153+53dupATGATG		intron	N/A	ENSP00000401705.1	Q96PC3-3

Frequencies

GnomAD3 genomes AF: 0.390 AC: 58744 AN: 150760 Hom.: 12520 Cov.: 0

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.408

GnomAD2 exomes AF: 0.429 AC: 86591 AN: 201824 AF XY: 0.441

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.361

Gnomad ASJ exome AF: 0.473

Gnomad EAS exome AF: 0.246

Gnomad FIN exome AF: 0.418

Gnomad NFE exome AF: 0.458

Gnomad OTH exome AF: 0.450

GnomAD4 exome AF: 0.449 AC: 631952 AN: 1407458 Hom.: 133803 Cov.: 32 AF XY: 0.453 AC XY: 317238 AN XY: 699748

African (AFR) AF: 0.233 AC: 7139 AN: 30642

American (AMR) AF: 0.342 AC: 13282 AN: 38786

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 11574 AN: 24490

East Asian (EAS) AF: 0.254 AC: 9833 AN: 38736

South Asian (SAS) AF: 0.559 AC: 44013 AN: 78714

European-Finnish (FIN) AF: 0.416 AC: 21321 AN: 51314

Middle Eastern (MID) AF: 0.468 AC: 2614 AN: 5580

European-Non Finnish (NFE) AF: 0.459 AC: 496631 AN: 1080890

Other (OTH) AF: 0.438 AC: 25545 AN: 58306

GnomAD4 genome AF: 0.389 AC: 58744 AN: 150880 Hom.: 12511 Cov.: 0 AF XY: 0.389 AC XY: 28674 AN XY: 73662

African (AFR) AF: 0.233 AC: 9577 AN: 41090

American (AMR) AF: 0.359 AC: 5423 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1637 AN: 3458

East Asian (EAS) AF: 0.232 AC: 1190 AN: 5122

South Asian (SAS) AF: 0.582 AC: 2759 AN: 4738

European-Finnish (FIN) AF: 0.424 AC: 4429 AN: 10434

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32327 AN: 67634

Other (OTH) AF: 0.406 AC: 852 AN: 2100

Alfa AF: 0.398 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: COSV57512127; COSMIC: COSV57512127;