rs10039749

Variant names:

• chr5-115892645-G-A
• rs10039749
• NM_001284.4:c.274-2442G>A

Variant summary

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

The NM_001284.4(AP3S1):​c.274-2442G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,876 control chromosomes in the GnomAD database, including 10,553 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 0.36 (10553 hom., cov: 31)
• Consequence: AP3S1 NM_001284.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575
• Publications: 1 publications found

Genes affected

AP3S1 (HGNC:2013): (adaptor related protein complex 3 subunit sigma 1) This gene encodes a subunit of the AP3 adaptor complex. This complex functions in the formation of subcellular vesicles budded from the Golgi body. Several related pseudogenes of this gene have been found. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3S1	NM_001284.4	c.274-2442G>A		intron_variant	Intron 3 of 5	ENST00000316788.12	NP_001275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3S1	ENST00000316788.12	c.274-2442G>A		intron_variant	Intron 3 of 5	1	NM_001284.4	ENSP00000325369.7

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55215 AN: 151758 Hom.: 10526 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.364 AC: 55303 AN: 151876 Hom.: 10553 Cov.: 31 AF XY: 0.367 AC XY: 27271 AN XY: 74234

African (AFR) AF: 0.447 AC: 18492 AN: 41400

American (AMR) AF: 0.440 AC: 6704 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1142 AN: 3468

East Asian (EAS) AF: 0.327 AC: 1686 AN: 5152

South Asian (SAS) AF: 0.340 AC: 1631 AN: 4800

European-Finnish (FIN) AF: 0.330 AC: 3481 AN: 10550

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21042 AN: 67952

Other (OTH) AF: 0.366 AC: 772 AN: 2108

Alfa AF: 0.354 Hom.: 1295

Bravo AF: 0.377

Asia WGS AF: 0.325 AC: 1132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.73
DANN	Benign	0.28
PhyloP100		-0.57
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: rs10039749; hg19: chr5-115228342; COSMIC: COSV57473984; COSMIC: COSV57473984;