Variant chr2-223765159-C-CCATCAT 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+53_429+54insATGATG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,558,338 control chromosomes in the GnomAD database, including 146,314 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.39 ( 12511 hom., cov: 0)

Exomes 𝑓: 0.45 ( 133803 hom. )

Consequence

AP1S3
NM_001039569.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.488

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 -10 ACMG points.

BP6

Variant 2-223765159-C-CCATCAT is Benign according to our data. Variant chr2-223765159-C-CCATCAT is described in ClinVar as [Benign]. Clinvar id is 2628169.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
AP1S3	NM_001039569.2 linkuse as main transcript	c.429+53_429+54insATGATG	intron_variant	ENST00000396654.7
AP1S3	XM_011510600.4 linkuse as main transcript	c.292-6410_292-6409insATGATG	intron_variant
AP1S3	NR_110905.2 linkuse as main transcript	n.600+53_600+54insATGATG	intron_variant, non_coding_transcript_variant
AP1S3	NR_110906.2 linkuse as main transcript	n.452+53_452+54insATGATG	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+53_429+54insATGATG		intron_variant		2	NM_001039569.2	P1	Q96PC3-4

Frequencies

GnomAD3 genomes

AF:

0.390

AC:

58744

AN:

150760

Hom.:

12520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.233

Gnomad SAS

AF:

0.583

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.408

GnomAD3 exomes

AF:

0.429

AC:

86591

AN:

201824

Hom.:

18024

AF XY:

0.441

AC XY:

48526

AN XY:

109964

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.361

Gnomad ASJ exome

AF:

0.473

Gnomad EAS exome

AF:

0.246

Gnomad SAS exome

AF:

0.584

Gnomad FIN exome

AF:

0.418

Gnomad NFE exome

AF:

0.458

Gnomad OTH exome

AF:

0.450

GnomAD4 exome

AF:

0.449

AC:

631952

AN:

1407458

Hom.:

133803

Cov.:

AF XY:

0.453

AC XY:

317238

AN XY:

699748

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.342

Gnomad4 ASJ exome

AF:

0.473

Gnomad4 EAS exome

AF:

0.254

Gnomad4 SAS exome

AF:

0.559

Gnomad4 FIN exome

AF:

0.416

Gnomad4 NFE exome

AF:

0.459

Gnomad4 OTH exome

AF:

0.438

GnomAD4 genome

AF:

0.389

AC:

58744

AN:

150880

Hom.:

12511

Cov.:

AF XY:

0.389

AC XY:

28674

AN XY:

73662

show subpopulations

Gnomad4 AFR

AF:

0.233

Gnomad4 AMR

AF:

0.359

Gnomad4 ASJ

AF:

0.473

Gnomad4 EAS

AF:

0.232

Gnomad4 SAS

AF:

0.582

Gnomad4 FIN

AF:

0.424

Gnomad4 NFE

AF:

0.478

Gnomad4 OTH

AF:

0.406

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 52% of patients studied by a panel of primary immunodeficiencies. Number of patients: 50. 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