chr2-223765156-A-ACACCAT

Variant names:

• chr2-223765156-A-ACACCAT
• NM_001039569.2:c.429+51_429+56dupATGGTG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001039569.2(AP1S3):​c.429+51_429+56dupATGGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000111 in 902,098 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: AP1S3 NM_001039569.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.814

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 2-223765156-A-ACACCAT is Benign according to our data. Variant chr2-223765156-A-ACACCAT is described in ClinVar as [Benign]. Clinvar id is 2688202.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP1S3	NM_001039569.2	c.429+51_429+56dupATGGTG		intron_variant	Intron 4 of 4	ENST00000396654.7	NP_001034658.1
AP1S3	XM_011510600.4	c.292-6412_292-6407dupATGGTG		intron_variant	Intron 3 of 3		XP_011508902.1
AP1S3	NR_110905.2	n.600+51_600+56dupATGGTG		intron_variant	Intron 5 of 5
AP1S3	NR_110906.2	n.452+51_452+56dupATGGTG		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP1S3	ENST00000396654.7	c.429+51_429+56dupATGGTG		intron_variant	Intron 4 of 4	2	NM_001039569.2	ENSP00000379891.2
ENSG00000286239	ENST00000650969.1	n.*1393+51_*1393+56dupATGGTG		intron_variant	Intron 16 of 16			ENSP00000498456.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000111 AC: 1 AN: 902098 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 449740

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000251

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

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: 34. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-224629873;