Variant chr2-223776146-C-T 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.183-137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 718,880 control chromosomes in the GnomAD database, including 6,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 2998 hom., cov: 33)

Exomes 𝑓: 0.087 ( 3542 hom. )

Consequence

AP1S3
NM_001039569.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.306

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=-0.84).

BP6

Variant 2-223776146-C-T is Benign according to our data. Variant chr2-223776146-C-T is described in ClinVar as [Benign]. Clinvar id is 2628301.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
AP1S3	NM_001039569.2 linkuse as main transcript	c.183-137G>A	intron_variant	ENST00000396654.7
AP1S3	XM_011510600.4 linkuse as main transcript	c.183-137G>A	intron_variant
AP1S3	NR_110905.2 linkuse as main transcript	n.315-137G>A	intron_variant, non_coding_transcript_variant
AP1S3	NR_110906.2 linkuse as main transcript	n.314+1545G>A	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.183-137G>A		intron_variant		2	NM_001039569.2	P1	Q96PC3-4

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23161

AN:

152040

Hom.:

2994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.0939

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.0868

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0465

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.117

AC:

18018

AN:

154208

Hom.:

1659

AF XY:

0.112

AC XY:

9212

AN XY:

81956

show subpopulations

Gnomad AFR exome

AF:

0.360

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.0919

Gnomad EAS exome

AF:

0.276

Gnomad SAS exome

AF:

0.141

Gnomad FIN exome

AF:

0.0818

Gnomad NFE exome

AF:

0.0448

Gnomad OTH exome

AF:

0.0886

GnomAD4 exome

AF:

0.0868

AC:

49175

AN:

566722

Hom.:

3542

Cov.:

AF XY:

0.0875

AC XY:

26765

AN XY:

305738

show subpopulations

Gnomad4 AFR exome

AF:

0.339

Gnomad4 AMR exome

AF:

0.158

Gnomad4 ASJ exome

AF:

0.0924

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.139

Gnomad4 FIN exome

AF:

0.0790

Gnomad4 NFE exome

AF:

0.0455

Gnomad4 OTH exome

AF:

0.0964

GnomAD4 genome

AF:

0.152

AC:

23190

AN:

152158

Hom.:

2998

Cov.:

AF XY:

0.155

AC XY:

11513

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.344

Gnomad4 AMR

AF:

0.135

Gnomad4 ASJ

AF:

0.0939

Gnomad4 EAS

AF:

0.254

Gnomad4 SAS

AF:

0.151

Gnomad4 FIN

AF:

0.0868

Gnomad4 NFE

AF:

0.0465

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.112

Hom.:

585

Bravo

AF:

0.167

Asia WGS

AF:

0.230

AC:

802

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 21% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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