Variant chr2-223765134-C-CT 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+78_429+79insA 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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.76

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 2-223765134-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	Effect	MANE
AP1S3	NM_001039569.2 linkuse as main transcript	c.429+78_429+79insA	intron_variant	ENST00000396654.7
AP1S3	XM_011510600.4 linkuse as main transcript	c.292-6385_292-6384insA	intron_variant
AP1S3	NR_110905.2 linkuse as main transcript	n.600+78_600+79insA	intron_variant, non_coding_transcript_variant
AP1S3	NR_110906.2 linkuse as main transcript	n.452+78_452+79insA	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+78_429+79insA		intron_variant		2	NM_001039569.2	P1	Q96PC3-4

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

30793

AN:

149672

Hom.:

5624

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0777

AC XY:

54572

AN XY:

702654

show subpopulations

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.:

AF XY:

0.211

AC XY:

15382

AN XY:

72992

show subpopulations

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

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 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

Name

Calibrated prediction

Score

Prediction

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

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