NM_001039569.2:c.429+78dupA

Variant names:

• chr2-223765134-C-CT
• rs11455542
• NM_001039569.2:c.429+78dupA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001039569.2(AP1S3):​c.429+78dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0897 in 1,565,024 control chromosomes in the GnomAD database, including 16,450 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (5638 hom., cov: 29)
  • Exomes 𝑓: 0.077 (10812 hom.)
• Consequence: AP1S3 NM_001039569.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.76

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]

ENSG00000286239 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-223765134-C-CT is Benign according to our data. Variant chr2-223765134-C-CT is described in ClinVar as [Benign]. Clinvar id is 2628220.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP1S3	NM_001039569.2	c.429+78dupA		intron_variant	Intron 4 of 4	ENST00000396654.7	NP_001034658.1
AP1S3	XM_011510600.4	c.292-6385dupA		intron_variant	Intron 3 of 3		XP_011508902.1
AP1S3	NR_110905.2	n.600+78dupA		intron_variant	Intron 5 of 5
AP1S3	NR_110906.2	n.452+78dupA		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP1S3	ENST00000396654.7	c.429+78dupA		intron_variant	Intron 4 of 4	2	NM_001039569.2	ENSP00000379891.2
ENSG00000286239	ENST00000650969.1	n.*1393+78dupA		intron_variant	Intron 16 of 16			ENSP00000498456.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 30793 AN: 149672 Hom.: 5624 Cov.: 29

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.113

Gnomad NFE AF: 0.0486

Gnomad OTH AF: 0.172

GnomAD3 exomes AF: 0.122 AC: 22269 AN: 182730 Hom.: 2605 AF XY: 0.111 AC XY: 11095 AN XY: 100216

Gnomad AFR exome AF: 0.436

Gnomad AMR exome AF: 0.221

Gnomad ASJ exome AF: 0.0585

Gnomad EAS exome AF: 0.346

Gnomad SAS exome AF: 0.120

Gnomad FIN exome AF: 0.0923

Gnomad NFE exome AF: 0.0413

Gnomad OTH exome AF: 0.0822

GnomAD4 exome AF: 0.0774 AC: 109602 AN: 1415234 Hom.: 10812 Cov.: 26 AF XY: 0.0777 AC XY: 54572 AN XY: 702654

Gnomad4 AFR exome AF: 0.480

Gnomad4 AMR exome AF: 0.254

Gnomad4 ASJ exome AF: 0.0704

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.0414

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.206 AC: 30843 AN: 149790 Hom.: 5638 Cov.: 29 AF XY: 0.211 AC XY: 15382 AN XY: 72992

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.0717

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.0485

Gnomad4 OTH AF: 0.170

Alfa AF: 0.113 Hom.: 465

Bravo AF: 0.226

Asia WGS AF: 0.298 AC: 1039 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 36% of patients studied by a panel of primary immunodeficiencies. Number of patients: 35. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11455542; hg19: chr2-224629851;