dbSNP rs1487720024: AP3S1:p.Ser24Ile (chr5-115866671-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001284.4(AP3S1):c.71G>T(p.Ser24Ile) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AP3S1
NM_001284.4 missense, splice_region

Scores

Splicing: ADA: 0.02591

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17

Publications

0 publications found

Variant links:

Genes affected

AP3S1 (HGNC:2013): (adaptor related protein complex 3 subunit sigma 1) This gene encodes a subunit of the AP3 adaptor complex. This complex functions in the formation of subcellular vesicles budded from the Golgi body. Several related pseudogenes of this gene have been found. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

AP3S1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3330419).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP3S1	NM_001284.4	MANE Select	c.71G>T	p.Ser24Ile	missense splice_region	Exon 2 of 6	NP_001275.1	Q92572
AP3S1	NM_001364119.1		c.71G>T	p.Ser24Ile	missense splice_region	Exon 2 of 7	NP_001351048.1
AP3S1	NM_001002924.3		c.5G>T	p.Ser2Ile	missense splice_region	Exon 3 of 7	NP_001002924.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP3S1	ENST00000316788.12	TSL:1 MANE Select	c.71G>T	p.Ser24Ile	missense splice_region	Exon 2 of 6	ENSP00000325369.7	Q92572
AP3S1	ENST00000395548.6	TSL:1	n.148G>T		splice_region non_coding_transcript_exon	Exon 3 of 7
AP3S1	ENST00000922028.1		c.221G>T	p.Ser74Ile	missense splice_region	Exon 2 of 6	ENSP00000592087.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1433986

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714616

African (AFR)

AF:

0.00

AC:

AN:

32604

American (AMR)

AF:

0.00

AC:

AN:

43226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25684

East Asian (EAS)

AF:

0.00

AC:

AN:

38898

South Asian (SAS)

AF:

0.00

AC:

AN:

83920

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53080

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5422

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091918

Other (OTH)

AF:

0.00

AC:

AN:

59234

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000330

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.030

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.37

MutationAssessor

Pathogenic

3.3

PhyloP100

6.2

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.34

Sift

Benign

0.097

Sift4G

Benign

0.11

Polyphen

0.14

Vest4

0.54

MutPred

0.56

Loss of disorder (P = 0.0023)

MVP

0.59

MPC

0.95

ClinPred

0.82

GERP RS

4.1

Varity_R

0.42

gMVP

0.50

Mutation Taster

=59/41

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.026

dbscSNV1_RF

Benign

0.24

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over