NM_005829.5:c.274-803A>C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3S2	NM_005829.5	c.274-803A>C		intron_variant	Intron 3 of 5	ENST00000336418.9	NP_005820.1
ARPIN-AP3S2	NM_001199058.2	c.877-803A>C		intron_variant	Intron 7 of 9		NP_001185987.1
AP3S2	NR_023361.2	n.438-803A>C		intron_variant	Intron 4 of 6
AP3S2	NR_037582.2	n.315-803A>C		intron_variant	Intron 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3S2	ENST00000336418.9	c.274-803A>C		intron_variant	Intron 3 of 5	1	NM_005829.5	ENSP00000338777.4
ARPIN-AP3S2	ENST00000398333.7	c.877-803A>C		intron_variant	Intron 7 of 9	2		ENSP00000381377.3

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

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.467

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.48
DANN	Benign	0.68

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

LitVar

Other links and lift over

dbSNP: rs2174292; hg19: chr15-90415581;