rs2290351

Positions:

• chr15-89831549-G-A
• chr15-89831549-G-C

Variant summary

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

The NM_005829.5(AP3S2):​c.*3966C>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 0.284 in 152,216 control chromosomes in the GnomAD database, including 6,728 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 (6726 hom., cov: 33)
  • Exomes 𝑓: 0.27 (2 hom.)
• Consequence: AP3S2 NM_005829.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.550

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=-0.85).
• 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.*3966C>T		3_prime_UTR_variant	6/6	ENST00000336418.9	NP_005820.1
ARPIN-AP3S2	NM_001199058.2	c.*3966C>T		3_prime_UTR_variant	10/10		NP_001185987.1
AP3S2	NR_023361.2	n.4712C>T		non_coding_transcript_exon_variant	7/7
AP3S2	NR_037582.2	n.4589C>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.*3966C>T		3_prime_UTR_variant	6/6	1	NM_005829.5	ENSP00000338777	P1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43206 AN: 152050 Hom.: 6720 Cov.: 33

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.264

GnomAD4 exome AF: 0.271 AC: 13 AN: 48 Hom.: 2 Cov.: 0 AF XY: 0.289 AC XY: 11 AN XY: 38

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.310

GnomAD4 genome AF: 0.284 AC: 43235 AN: 152168 Hom.: 6726 Cov.: 33 AF XY: 0.289 AC XY: 21504 AN XY: 74390

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.577

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.270

Alfa AF: 0.235 Hom.: 7688

Bravo AF: 0.292

Asia WGS AF: 0.384 AC: 1334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.52

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: rs2290351; hg19: chr15-90374781;