Genetic Variant AP3S2:c.*3966C>T (chr15-89831549-G-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.*3966C>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 0.284 in 152,216 control chromosomes in the GnomAD database, including 6,728 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 0.28 ( 6726 hom., cov: 33)

Exomes 𝑓: 0.27 ( 2 hom. )

Consequence

AP3S2
NM_005829.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.550

Publications

15 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:

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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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005829.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AP3S2	NM_005829.5	MANE Select	c.*3966C>T	3_prime_UTR	Exon 6 of 6	NP_005820.1	P59780-1
ARPIN-AP3S2	NM_001199058.2		c.*3966C>T	3_prime_UTR	Exon 10 of 10	NP_001185987.1
AP3S2	NR_023361.2		n.4712C>T	non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3S2	ENST00000336418.9	TSL:1 MANE Select	c.*3966C>T		3_prime_UTR	Exon 6 of 6	ENSP00000338777.4	P59780-1

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43206

AN:

152050

Hom.:

6720

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.315

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.577

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.314

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.264

GnomAD4 exome

AF:

0.271

AC:

AN:

Hom.:

Cov.:

AF XY:

0.289

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.310

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.284

AC:

43235

AN:

152168

Hom.:

6726

Cov.:

AF XY:

0.289

AC XY:

21504

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.350

AC:

14547

AN:

41506

American (AMR)

AF:

0.316

AC:

4827

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

700

AN:

3472

East Asian (EAS)

AF:

0.577

AC:

2985

AN:

5170

South Asian (SAS)

AF:

0.200

AC:

961

AN:

4816

European-Finnish (FIN)

AF:

0.314

AC:

3321

AN:

10588

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

15033

AN:

67996

Other (OTH)

AF:

0.270

AC:

571

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1587

3175

4762

6350

7937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.247

Hom.:

14849

Bravo

AF:

0.292

Asia WGS

AF:

0.384

AC:

1334

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.6

(source)

DANN

Benign

0.52

PhyloP100

0.55

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over