dbSNP rs2028299: AP3S2:c.*4490G>T (chr15-89831025-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005829.5(AP3S2):c.*4490G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 153,066 control chromosomes in the GnomAD database, including 40,159 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.72 ( 39936 hom., cov: 32)

Exomes 𝑓: 0.67 ( 223 hom. )

Consequence

AP3S2
NM_005829.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.653

Publications

106 publications found

Variant links:

Genes affected

AP3S2 (HGNC:571): (adaptor related protein complex 3 subunit sigma 2) Predicted to be involved in anterograde synaptic vesicle transport and vesicle-mediated transport. Located in intracellular membrane-bounded organelle. Part of AP-3 adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]

AP3S2 links:

ARPIN-AP3S2 (HGNC:38824): (ARPIN-AP3S2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring C15orf38 (chromosome 15 open reading frame 38) and AP3S2 (adaptor-related protein complex 3, sigma 2 subunit) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

ARPIN-AP3S2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AP3S2	NM_005829.5 link	c.*4490G>T	3_prime_UTR_variant	Exon 6 of 6	ENST00000336418.9	NP_005820.1	P59780-1A0A024RC62
AP3S2	NR_023361.2 link	n.5236G>T	non_coding_transcript_exon_variant	Exon 7 of 7
AP3S2	NR_037582.2 link	n.5113G>T	non_coding_transcript_exon_variant	Exon 6 of 6
ARPIN-AP3S2	NM_001199058.2 link	c.*4490G>T	3_prime_UTR_variant	Exon 10 of 10		NP_001185987.1	A0A0A6YYH1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3S2	ENST00000336418.9 link	c.*4490G>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_005829.5	ENSP00000338777.4		P59780-1

Frequencies

GnomAD3 genomes

AF:

0.723

AC:

109902

AN:

151990

Hom.:

39877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.693

Gnomad AMI

AF:

0.747

Gnomad AMR

AF:

0.782

Gnomad ASJ

AF:

0.750

Gnomad EAS

AF:

0.799

Gnomad SAS

AF:

0.675

Gnomad FIN

AF:

0.742

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.721

Gnomad OTH

AF:

0.735

GnomAD4 exome

AF:

0.672

AC:

644

AN:

958

Hom.:

223

Cov.:

AF XY:

0.680

AC XY:

355

AN XY:

522

show subpopulations

African (AFR)

AF:

0.536

AC:

AN:

American (AMR)

AF:

0.800

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.833

AC:

AN:

East Asian (EAS)

AF:

0.656

AC:

AN:

122

South Asian (SAS)

AF:

0.625

AC:

AN:

European-Finnish (FIN)

AF:

0.729

AC:

102

AN:

140

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

376

AN:

564

Other (OTH)

AF:

0.571

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.723

AC:

110027

AN:

152108

Hom.:

39936

Cov.:

AF XY:

0.728

AC XY:

54132

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.694

AC:

28787

AN:

41502

American (AMR)

AF:

0.782

AC:

11959

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

2601

AN:

3468

East Asian (EAS)

AF:

0.800

AC:

4134

AN:

5168

South Asian (SAS)

AF:

0.677

AC:

3263

AN:

4820

European-Finnish (FIN)

AF:

0.742

AC:

7849

AN:

10574

Middle Eastern (MID)

AF:

0.728

AC:

214

AN:

294

European-Non Finnish (NFE)

AF:

0.721

AC:

48982

AN:

67972

Other (OTH)

AF:

0.739

AC:

1557

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1584

3167

4751

6334

7918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

838

1676

2514

3352

4190

<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:

0.724

Hom.:

120720

Bravo

AF:

0.730

Asia WGS

AF:

0.745

AC:

2589

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.30

(source)

DANN

Benign

0.55

PhyloP100

-0.65

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over