Variant chr5-115913381-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001284.4(AP3S1):c.473C>T(p.Pro158Leu) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.39 ( 0 hom., cov: 39)

Exomes 𝑓: 0.48 ( 10 hom. )

Failed GnomAD Quality Control

Consequence

AP3S1
NM_001284.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.81

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027187169).

BP6

Variant 5-115913381-C-T is Benign according to our data. Variant chr5-115913381-C-T is described in ClinVar as [Benign]. Clinvar id is 769304.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP3S1	NM_001284.4 linkuse as main transcript	c.473C>T	p.Pro158Leu	missense_variant	6/6	ENST00000316788.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
AP3S1	ENST00000316788.12 linkuse as main transcript	c.473C>T	p.Pro158Leu	missense_variant	6/6	1	NM_001284.4	P1
AP3S1	ENST00000395548.6 linkuse as main transcript	n.550C>T		non_coding_transcript_exon_variant	7/7	1
AP3S1	ENST00000505423.1 linkuse as main transcript	n.92C>T		non_coding_transcript_exon_variant	2/2	2
AP3S1	ENST00000506430.2 linkuse as main transcript	c.*73C>T		3_prime_UTR_variant, NMD_transcript_variant	8/8	5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

29834

AN:

76788

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.342

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.391

Gnomad EAS

AF:

0.309

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.397

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.399

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.479

AC:

457274

AN:

954664

Hom.:

Cov.:

AF XY:

0.481

AC XY:

233976

AN XY:

486882

show subpopulations

Gnomad4 AFR exome

AF:

0.488

Gnomad4 AMR exome

AF:

0.491

Gnomad4 ASJ exome

AF:

0.490

Gnomad4 EAS exome

AF:

0.453

Gnomad4 SAS exome

AF:

0.491

Gnomad4 FIN exome

AF:

0.494

Gnomad4 NFE exome

AF:

0.478

Gnomad4 OTH exome

AF:

0.480

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.389

AC:

29880

AN:

76888

Hom.:

Cov.:

AF XY:

0.384

AC XY:

14580

AN XY:

37976

show subpopulations

Gnomad4 AFR

AF:

0.391

Gnomad4 AMR

AF:

0.377

Gnomad4 ASJ

AF:

0.391

Gnomad4 EAS

AF:

0.311

Gnomad4 SAS

AF:

0.390

Gnomad4 FIN

AF:

0.382

Gnomad4 NFE

AF:

0.396

Gnomad4 OTH

AF:

0.399

Alfa

AF:

0.463

Hom.:

ExAC

AF:

0.469

AC:

56993

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

8.1e-10

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.28

Sift

Benign

0.052

Sift4G

Benign

0.20

Polyphen

0.047

Vest4

0.22

MPC

0.72

ClinPred

0.036

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.24

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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