rs7174330

Positions:

• chr15-89891347-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP3S2	NM_005829.5	c.70-2207T>C		intron_variant		ENST00000336418.9	NP_005820.1
ARPIN-AP3S2	NM_001199058.2	c.673-2207T>C		intron_variant			NP_001185987.1
AP3S2	NR_023361.2	n.115-2207T>C		intron_variant, non_coding_transcript_variant
AP3S2	NR_037582.2	n.115-2211T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP3S2	ENST00000336418.9	c.70-2207T>C		intron_variant		1	NM_005829.5	ENSP00000338777	P1

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

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.479

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.8
DANN	Benign	0.75

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: rs7174330; hg19: chr15-90434579;