15-89872349-T-G

Variant names:

• chr15-89872349-T-G
• rs2174292
• NM_005829.5:c.274-803A>C

Variant summary

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

The NM_005829.5(AP3S2):​c.274-803A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,898 control chromosomes in the GnomAD database, including 14,978 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 0.44 (14978 hom., cov: 31)
• Consequence: AP3S2 NM_005829.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3S2	NM_005829.5	MANE Select	c.274-803A>C		intron	N/A	NP_005820.1	P59780-1
	ARPIN-AP3S2	NM_001199058.2		c.877-803A>C		intron	N/A	NP_001185987.1
	AP3S2	NR_023361.2		n.438-803A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3S2	ENST00000336418.9	TSL:1 MANE Select	c.274-803A>C		intron	N/A	ENSP00000338777.4	P59780-1
	ARPIN-AP3S2	ENST00000398333.7	TSL:2	c.877-803A>C		intron	N/A	ENSP00000381377.3
	AP3S2	ENST00000558806.5	TSL:1	n.*159-803A>C		intron	N/A	ENSP00000454027.1	H0YNI6

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66620 AN: 151782 Hom.: 14973 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.439 AC: 66644 AN: 151898 Hom.: 14978 Cov.: 31 AF XY: 0.444 AC XY: 32947 AN XY: 74236

African (AFR) AF: 0.389 AC: 16120 AN: 41424

American (AMR) AF: 0.563 AC: 8593 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1708 AN: 3464

East Asian (EAS) AF: 0.629 AC: 3256 AN: 5176

South Asian (SAS) AF: 0.340 AC: 1640 AN: 4824

European-Finnish (FIN) AF: 0.453 AC: 4758 AN: 10510

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29060 AN: 67920

Other (OTH) AF: 0.467 AC: 983 AN: 2104

Alfa AF: 0.438 Hom.: 1818

Bravo AF: 0.452

Asia WGS AF: 0.469 AC: 1629 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.48
DANN	Benign	0.68
PhyloP100		-1.0
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: rs2174292; hg19: chr15-90415581;