Variant chr2-223773250-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001039569.2(AP1S3):c.291+2651T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,281,004 control chromosomes in the GnomAD database, including 21,256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 8403 hom., cov: 32)

Exomes 𝑓: 0.11 ( 12853 hom. )

Consequence

AP1S3
NM_001039569.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.251

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-223773250-A-G is Benign according to our data. Variant chr2-223773250-A-G is described in ClinVar as [Benign]. Clinvar id is 2628198.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
AP1S3	NM_001039569.2 linkuse as main transcript	c.291+2651T>C	intron_variant	ENST00000396654.7
AP1S3	XM_011510600.4 linkuse as main transcript	c.291+2651T>C	intron_variant
AP1S3	NR_110905.2 linkuse as main transcript	n.462+63T>C	intron_variant, non_coding_transcript_variant
AP1S3	NR_110906.2 linkuse as main transcript	n.314+4441T>C	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.291+2651T>C		intron_variant		2	NM_001039569.2	P1	Q96PC3-4

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39669

AN:

151912

Hom.:

8378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.542

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.583

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.0832

Gnomad OTH

AF:

0.238

GnomAD4 exome

AF:

0.109

AC:

122673

AN:

1128974

Hom.:

12853

AF XY:

0.110

AC XY:

60908

AN XY:

553358

show subpopulations

Gnomad4 AFR exome

AF:

0.563

Gnomad4 AMR exome

AF:

0.403

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.596

Gnomad4 SAS exome

AF:

0.182

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.0743

Gnomad4 OTH exome

AF:

0.155

GnomAD4 genome

AF:

0.261

AC:

39748

AN:

152030

Hom.:

8403

Cov.:

AF XY:

0.266

AC XY:

19789

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.543

Gnomad4 AMR

AF:

0.328

Gnomad4 ASJ

AF:

0.129

Gnomad4 EAS

AF:

0.582

Gnomad4 SAS

AF:

0.213

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.0831

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.227

Hom.:

1021

Bravo

AF:

0.294

Asia WGS

AF:

0.422

AC:

1468

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 45% of patients studied by a panel of primary immunodeficiencies. Number of patients: 43. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.7

DANN

Benign

0.34

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