15-89880061-T-C

Variant names:

• chr15-89880061-T-C
• rs4932265
• NM_005829.5:c.273+8460A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005829.5(AP3S2):​c.273+8460A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 150,220 control chromosomes in the GnomAD database, including 43,473 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 0.76 (43473 hom., cov: 24)
• Consequence: AP3S2 NM_005829.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.643
• Publications: 16 publications found

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3S2	NM_005829.5	MANE Select	c.273+8460A>G		intron	N/A	NP_005820.1
	ARPIN-AP3S2	NM_001199058.2		c.876+8460A>G		intron	N/A	NP_001185987.1
	AP3S2	NR_023361.2		n.319-2637A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3S2	ENST00000336418.9	TSL:1 MANE Select	c.273+8460A>G		intron	N/A	ENSP00000338777.4
	ARPIN-AP3S2	ENST00000398333.7	TSL:2	c.876+8460A>G		intron	N/A	ENSP00000381377.3
	AP3S2	ENST00000558806.5	TSL:1	n.*158+8460A>G		intron	N/A	ENSP00000454027.1

Frequencies

GnomAD3 genomes AF: 0.760 AC: 114049 AN: 150102 Hom.: 43416 Cov.: 24

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.771

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.760 AC: 114171 AN: 150220 Hom.: 43473 Cov.: 24 AF XY: 0.763 AC XY: 55954 AN XY: 73334

African (AFR) AF: 0.782 AC: 31999 AN: 40922

American (AMR) AF: 0.798 AC: 12032 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2644 AN: 3462

East Asian (EAS) AF: 0.804 AC: 4048 AN: 5036

South Asian (SAS) AF: 0.688 AC: 3243 AN: 4716

European-Finnish (FIN) AF: 0.752 AC: 7649 AN: 10168

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50013 AN: 67556

Other (OTH) AF: 0.775 AC: 1616 AN: 2086

Alfa AF: 0.763 Hom.: 5831

Bravo AF: 0.770

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.45
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4932265; hg19: chr15-90423293;