Genetic Variant AP1S3:p.Ser158Ser (chr2-223752845-T-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The ENST00000443700.5(AP1S3):c.474A>G(p.Ser158Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 330,840 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 1 hom., cov: 30)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

AP1S3
ENST00000443700.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.665

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

psoriasis 15, pustular, susceptibility to
Inheritance: AD Classification: STRONG Submitted by: G2P
pustulosis palmaris et plantaris
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
psoriasis 14, pustular
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

AP1S3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 2-223752845-T-C is Benign according to our data. Variant chr2-223752845-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2651946.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.665 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000443700.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP1S3	ENST00000443700.5	TSL:1	c.474A>G	p.Ser158Ser	synonymous	Exon 5 of 5	ENSP00000397155.1	Q96PC3-2
AP1S3	ENST00000699384.1		n.577-10855A>G		intron	N/A
AP1S3	ENST00000699385.1		n.*304-10855A>G		intron	N/A	ENSP00000514349.1	A0A8V8TPZ3

Frequencies

GnomAD3 genomes

AF:

0.00408

AC:

618

AN:

151630

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000788

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00288

GnomAD2 exomes

AF:

0.000325

AC:

AN:

52384

AF XY:

0.000227

show subpopulations

Gnomad AFR exome

AF:

0.0146

Gnomad AMR exome

AF:

0.000380

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000700

GnomAD4 exome

AF:

0.000212

AC:

AN:

179092

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

AN XY:

108844

show subpopulations

African (AFR)

AF:

0.0119

AC:

AN:

1930

American (AMR)

AF:

0.000561

AC:

AN:

10702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7026

East Asian (EAS)

AF:

0.00

AC:

AN:

2424

South Asian (SAS)

AF:

0.0000257

AC:

AN:

38978

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8870

Middle Eastern (MID)

AF:

0.00

AC:

AN:

618

European-Non Finnish (NFE)

AF:

0.0000298

AC:

AN:

100680

Other (OTH)

AF:

0.000636

AC:

AN:

7864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00410

AC:

622

AN:

151748

Hom.:

Cov.:

AF XY:

0.00410

AC XY:

304

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.0145

AC:

600

AN:

41348

American (AMR)

AF:

0.000787

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4786

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10494

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67920

Other (OTH)

AF:

0.00285

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

120

150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00221

Hom.:

Bravo

AF:

0.00458

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.34

(source)

DANN

Benign

0.42

PhyloP100

-0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over