rs4932145

Positions:

• chr15-89833227-G-A

Variant summary

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

The NM_005829.5(AP3S2):​c.*2288C>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 0.281 in 152,040 control chromosomes in the GnomAD database, including 6,542 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 (6541 hom., cov: 31)
  • Exomes 𝑓: 0.30 (1 hom.)
• Consequence: AP3S2 NM_005829.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP3S2	NM_005829.5	c.*2288C>T		3_prime_UTR_variant	6/6	ENST00000336418.9	NP_005820.1
ARPIN-AP3S2	NM_001199058.2	c.*2288C>T		3_prime_UTR_variant	10/10		NP_001185987.1
AP3S2	NR_023361.2	n.3034C>T		non_coding_transcript_exon_variant	7/7
AP3S2	NR_037582.2	n.2911C>T		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP3S2	ENST00000336418.9	c.*2288C>T		3_prime_UTR_variant	6/6	1	NM_005829.5	ENSP00000338777	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42648 AN: 151912 Hom.: 6534 Cov.: 31

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.300 AC: 3 AN: 10 Hom.: 1 Cov.: 0 AF XY: 0.300 AC XY: 3 AN XY: 10

Gnomad4 AMR exome AF: 1.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.281 AC: 42681 AN: 152030 Hom.: 6541 Cov.: 31 AF XY: 0.286 AC XY: 21238 AN XY: 74332

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.578

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.264

Alfa AF: 0.230 Hom.: 5460

Bravo AF: 0.288

Asia WGS AF: 0.387 AC: 1345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.19
DANN	Benign	0.65

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: rs4932145; hg19: chr15-90376459;