Variant chr2-223837588-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000443700.5(AP1S3):c.-138C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 472,094 control chromosomes in the GnomAD database, including 30,243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.35 ( 9499 hom., cov: 30)

Exomes 𝑓: 0.35 ( 20744 hom. )

Consequence

AP1S3
ENST00000443700.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.234

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-223837588-G-C is Benign according to our data. Variant chr2-223837588-G-C is described in ClinVar as [Benign]. Clinvar id is 2688440.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	Effect	MANE
AP1S3	NM_001039569.2 linkuse as main transcript	upstream_gene_variant	ENST00000396654.7
AP1S3	XM_011510600.4 linkuse as main transcript	upstream_gene_variant
AP1S3	NR_110905.2 linkuse as main transcript	upstream_gene_variant
AP1S3	NR_110906.2 linkuse as main transcript	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP1S3	ENST00000396654.7 linkuse as main transcript			upstream_gene_variant		2	NM_001039569.2	P1	Q96PC3-4

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52608

AN:

151716

Hom.:

9491

Cov.:

show subpopulations

Gnomad AFR

AF:

0.368

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.0555

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.366

GnomAD4 exome

AF:

0.349

AC:

111793

AN:

320270

Hom.:

20744

Cov.:

AF XY:

0.351

AC XY:

56546

AN XY:

161062

show subpopulations

Gnomad4 AFR exome

AF:

0.363

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.417

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.265

Gnomad4 FIN exome

AF:

0.322

Gnomad4 NFE exome

AF:

0.376

Gnomad4 OTH exome

AF:

0.356

GnomAD4 genome

AF:

0.347

AC:

52636

AN:

151824

Hom.:

9499

Cov.:

AF XY:

0.341

AC XY:

25316

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.368

Gnomad4 AMR

AF:

0.303

Gnomad4 ASJ

AF:

0.411

Gnomad4 EAS

AF:

0.0549

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.297

Gnomad4 NFE

AF:

0.373

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.218

Hom.:

499

Bravo

AF:

0.349

Asia WGS

AF:

0.201

AC:

702

AN:

3474

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

Jan 24, 2024

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: 35. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.3

DANN

Benign

0.86

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