Variant chr2-223765159-C-CCAT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001039569.2(AP1S3):c.429+53_429+54insATG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0935 in 1,529,558 control chromosomes in the GnomAD database, including 16,098 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 6552 hom., cov: 0)

Exomes 𝑓: 0.080 ( 9546 hom. )

Consequence

AP1S3
NM_001039569.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.488

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 2-223765159-C-CCAT is Benign according to our data. Variant chr2-223765159-C-CCAT is described in ClinVar as [Benign]. Clinvar id is 2628211.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
AP1S3	NM_001039569.2 linkuse as main transcript	c.429+53_429+54insATG	intron_variant	ENST00000396654.7
AP1S3	XM_011510600.4 linkuse as main transcript	c.292-6410_292-6409insATG	intron_variant
AP1S3	NR_110905.2 linkuse as main transcript	n.600+53_600+54insATG	intron_variant, non_coding_transcript_variant
AP1S3	NR_110906.2 linkuse as main transcript	n.452+53_452+54insATG	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP1S3	ENST00000396654.7 linkuse as main transcript	c.429+53_429+54insATG		intron_variant		2	NM_001039569.2	P1	Q96PC3-4

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32544

AN:

150776

Hom.:

6536

Cov.:

show subpopulations

Gnomad AFR

AF:

0.515

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.0717

Gnomad EAS

AF:

0.411

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0483

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.129

AC:

25962

AN:

201824

Hom.:

2734

AF XY:

0.117

AC XY:

12896

AN XY:

109964

show subpopulations

Gnomad AFR exome

AF:

0.473

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.0664

Gnomad EAS exome

AF:

0.344

Gnomad SAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.0983

Gnomad NFE exome

AF:

0.0448

Gnomad OTH exome

AF:

0.0893

GnomAD4 exome

AF:

0.0801

AC:

110442

AN:

1378662

Hom.:

9546

Cov.:

AF XY:

0.0804

AC XY:

55119

AN XY:

685164

show subpopulations

Gnomad4 AFR exome

AF:

0.501

Gnomad4 AMR exome

AF:

0.251

Gnomad4 ASJ exome

AF:

0.0733

Gnomad4 EAS exome

AF:

0.369

Gnomad4 SAS exome

AF:

0.147

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.0436

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.216

AC:

32602

AN:

150896

Hom.:

6552

Cov.:

AF XY:

0.220

AC XY:

16202

AN XY:

73678

show subpopulations

Gnomad4 AFR

AF:

0.514

Gnomad4 AMR

AF:

0.223

Gnomad4 ASJ

AF:

0.0717

Gnomad4 EAS

AF:

0.411

Gnomad4 SAS

AF:

0.162

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.0483

Gnomad4 OTH

AF:

0.172

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 40% of patients studied by a panel of primary immunodeficiencies. Number of patients: 38. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over