NM_005829.5:c.*2288C>T

Variant names:

• chr15-89833227-G-A
• rs4932145
• NM_005829.5:c.*2288C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3S2	NM_005829.5	MANE Select	c.*2288C>T		3_prime_UTR	Exon 6 of 6	NP_005820.1
	AP3S2	NR_023361.2		n.3034C>T		non_coding_transcript_exon	Exon 7 of 7
	AP3S2	NR_037582.2		n.2911C>T		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3S2	ENST00000336418.9	TSL:1 MANE Select	c.*2288C>T		3_prime_UTR	Exon 6 of 6	ENSP00000338777.4

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.338 AC: 14001 AN: 41424

American (AMR) AF: 0.314 AC: 4798 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 731 AN: 3470

East Asian (EAS) AF: 0.578 AC: 2986 AN: 5170

South Asian (SAS) AF: 0.196 AC: 944 AN: 4814

European-Finnish (FIN) AF: 0.314 AC: 3321 AN: 10572

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15051 AN: 67980

Other (OTH) AF: 0.264 AC: 559 AN: 2114

Alfa AF: 0.235 Hom.: 7347

Bravo AF: 0.288

Asia WGS AF: 0.387 AC: 1345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.19
DANN	Benign	0.65
PhyloP100		-2.4
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: rs4932145; hg19: chr15-90376459;