Variant chr2-223776086-C-CAA 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.183-78_183-77insTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,041,924 control chromosomes in the GnomAD database, including 30,782 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.23 ( 3938 hom., cov: 25)

Exomes 𝑓: 0.24 ( 26844 hom. )

Consequence

AP1S3
NM_001039569.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.413

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 2-223776086-C-CAA is Benign according to our data. Variant chr2-223776086-C-CAA is described in ClinVar as [Benign]. Clinvar id is 2628237.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
AP1S3	NM_001039569.2 linkuse as main transcript	c.183-78_183-77insTT	intron_variant	ENST00000396654.7
AP1S3	XM_011510600.4 linkuse as main transcript	c.183-78_183-77insTT	intron_variant
AP1S3	NR_110905.2 linkuse as main transcript	n.315-78_315-77insTT	intron_variant, non_coding_transcript_variant
AP1S3	NR_110906.2 linkuse as main transcript	n.314+1604_314+1605insTT	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.183-78_183-77insTT		intron_variant		2	NM_001039569.2	P1	Q96PC3-4

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34371

AN:

151884

Hom.:

3931

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.217

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.223

GnomAD3 exomes

AF:

0.210

AC:

33479

AN:

159596

Hom.:

3707

AF XY:

0.211

AC XY:

17845

AN XY:

84432

show subpopulations

Gnomad AFR exome

AF:

0.222

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.234

Gnomad EAS exome

AF:

0.179

Gnomad SAS exome

AF:

0.168

Gnomad FIN exome

AF:

0.202

Gnomad NFE exome

AF:

0.252

Gnomad OTH exome

AF:

0.217

GnomAD4 exome

AF:

0.241

AC:

214269

AN:

889922

Hom.:

26844

Cov.:

AF XY:

0.239

AC XY:

110128

AN XY:

459942

show subpopulations

Gnomad4 AFR exome

AF:

0.228

Gnomad4 AMR exome

AF:

0.156

Gnomad4 ASJ exome

AF:

0.233

Gnomad4 EAS exome

AF:

0.212

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.260

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.226

AC:

34416

AN:

152002

Hom.:

3938

Cov.:

AF XY:

0.222

AC XY:

16503

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.221

Gnomad4 AMR

AF:

0.200

Gnomad4 ASJ

AF:

0.241

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.160

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.238

Hom.:

784

Bravo

AF:

0.227

Asia WGS

AF:

0.187

AC:

650

AN:

3478

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 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 30. 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