rs7174330

Variant names:

• chr15-89891347-A-G
• rs7174330
• NM_005829.5:c.70-2207T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005829.5(AP3S2):​c.70-2207T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,994 control chromosomes in the GnomAD database, including 16,535 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 0.46 (16535 hom., cov: 32)
• Consequence: AP3S2 NM_005829.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.586 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3S2	NM_005829.5	MANE Select	c.70-2207T>C		intron	N/A	NP_005820.1	P59780-1
	ARPIN-AP3S2	NM_001199058.2		c.673-2207T>C		intron	N/A	NP_001185987.1
	AP3S2	NR_023361.2		n.115-2207T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3S2	ENST00000336418.9	TSL:1 MANE Select	c.70-2207T>C		intron	N/A	ENSP00000338777.4	P59780-1
	ARPIN-AP3S2	ENST00000398333.7	TSL:2	c.673-2207T>C		intron	N/A	ENSP00000381377.3
	AP3S2	ENST00000558806.5	TSL:1	n.70-2211T>C		intron	N/A	ENSP00000454027.1	H0YNI6

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70400 AN: 151876 Hom.: 16513 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.477

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.464 AC: 70472 AN: 151994 Hom.: 16535 Cov.: 32 AF XY: 0.467 AC XY: 34700 AN XY: 74258

African (AFR) AF: 0.481 AC: 19922 AN: 41430

American (AMR) AF: 0.559 AC: 8534 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1712 AN: 3468

East Asian (EAS) AF: 0.604 AC: 3125 AN: 5174

South Asian (SAS) AF: 0.346 AC: 1670 AN: 4824

European-Finnish (FIN) AF: 0.452 AC: 4769 AN: 10548

Middle Eastern (MID) AF: 0.497 AC: 144 AN: 290

European-Non Finnish (NFE) AF: 0.430 AC: 29200 AN: 67978

Other (OTH) AF: 0.479 AC: 1013 AN: 2114

Alfa AF: 0.454 Hom.: 1938

Bravo AF: 0.479

Asia WGS AF: 0.487 AC: 1694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.8
DANN	Benign	0.75
PhyloP100		0.18
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: rs7174330; hg19: chr15-90434579;