rs2028299

Positions:

• chr15-89831025-C-A
• chr15-89831025-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653

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:):

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 = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP3S2	NM_005829.5	c.*4490G>T		3_prime_UTR_variant	6/6	ENST00000336418.9
ARPIN-AP3S2	NM_001199058.2	c.*4490G>T		3_prime_UTR_variant	10/10
AP3S2	NR_023361.2	n.5236G>T		non_coding_transcript_exon_variant	7/7
AP3S2	NR_037582.2	n.5113G>T		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP3S2	ENST00000336418.9	c.*4490G>T		3_prime_UTR_variant	6/6	1	NM_005829.5	P1

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109902 AN: 151990 Hom.: 39877 Cov.: 32

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.: 0 AF XY: 0.680 AC XY: 355 AN XY: 522

Gnomad4 AFR exome AF: 0.536

Gnomad4 AMR exome AF: 0.800

Gnomad4 ASJ exome AF: 0.833

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.625

Gnomad4 FIN exome AF: 0.729

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.571

GnomAD4 genome AF: 0.723 AC: 110027 AN: 152108 Hom.: 39936 Cov.: 32 AF XY: 0.728 AC XY: 54132 AN XY: 74356

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.739

Alfa AF: 0.724 Hom.: 53165

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
DANN	Benign	0.55

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: rs2028299; hg19: chr15-90374257;