chr2-223765159-C-CCATCATCAT

Variant names:

• chr2-223765159-C-CCATCATCAT
• rs10644138
• NM_001039569.2:c.429+45_429+53dupATGATGATG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001039569.2(AP1S3):​c.429+45_429+53dupATGATGATG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0037 in 1,560,316 control chromosomes in the GnomAD database, including 22 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0038 (21 hom.)
• Consequence: AP1S3 NM_001039569.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 481 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP1S3	NM_001039569.2	c.429+45_429+53dupATGATGATG		intron_variant	Intron 4 of 4	ENST00000396654.7	NP_001034658.1
AP1S3	XM_011510600.4	c.292-6418_292-6410dupATGATGATG		intron_variant	Intron 3 of 3		XP_011508902.1
AP1S3	NR_110905.2	n.600+45_600+53dupATGATGATG		intron_variant	Intron 5 of 5
AP1S3	NR_110906.2	n.452+45_452+53dupATGATGATG		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP1S3	ENST00000396654.7	c.429+45_429+53dupATGATGATG		intron_variant	Intron 4 of 4	2	NM_001039569.2	ENSP00000379891.2
ENSG00000286239	ENST00000650969.1	n.*1393+45_*1393+53dupATGATGATG		intron_variant	Intron 16 of 16			ENSP00000498456.1

Frequencies

GnomAD3 genomes AF: 0.00319 AC: 482 AN: 150902 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00154

Gnomad AMI AF: 0.00221

Gnomad AMR AF: 0.00516

Gnomad ASJ AF: 0.00405

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.00190

Gnomad FIN AF: 0.00105

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00424

Gnomad OTH AF: 0.00626

GnomAD3 exomes AF: 0.00340 AC: 686 AN: 201824 Hom.: 9 AF XY: 0.00356 AC XY: 392 AN XY: 109964

Gnomad AFR exome AF: 0.00103

Gnomad AMR exome AF: 0.00267

Gnomad ASJ exome AF: 0.00281

Gnomad EAS exome AF: 0.000795

Gnomad SAS exome AF: 0.00217

Gnomad FIN exome AF: 0.00128

Gnomad NFE exome AF: 0.00491

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00375 AC: 5291 AN: 1409294 Hom.: 21 Cov.: 32 AF XY: 0.00377 AC XY: 2643 AN XY: 700672

Gnomad4 AFR exome AF: 0.00169

Gnomad4 AMR exome AF: 0.00312

Gnomad4 ASJ exome AF: 0.00224

Gnomad4 EAS exome AF: 0.000490

Gnomad4 SAS exome AF: 0.00209

Gnomad4 FIN exome AF: 0.00185

Gnomad4 NFE exome AF: 0.00410

Gnomad4 OTH exome AF: 0.00427

GnomAD4 genome AF: 0.00318 AC: 481 AN: 151022 Hom.: 1 Cov.: 0 AF XY: 0.00311 AC XY: 229 AN XY: 73736

Gnomad4 AFR AF: 0.00153

Gnomad4 AMR AF: 0.00522

Gnomad4 ASJ AF: 0.00405

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.00169

Gnomad4 FIN AF: 0.00105

Gnomad4 NFE AF: 0.00423

Gnomad4 OTH AF: 0.00618

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10644138; hg19: chr2-224629876;