rs3756555

Variant names:

• chr5-115908239-G-A
• rs3756555
• NM_001284.4:c.454-5123G>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.454-5123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,854 control chromosomes in the GnomAD database, including 12,147 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 0.40 (12147 hom., cov: 32)
• Consequence: AP3S1 NM_001284.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3S1	NM_001284.4	c.454-5123G>A		intron_variant	Intron 5 of 5	ENST00000316788.12	NP_001275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3S1	ENST00000316788.12	c.454-5123G>A		intron_variant	Intron 5 of 5	1	NM_001284.4	ENSP00000325369.7
AP3S1	ENST00000395548.6	n.531-5123G>A		intron_variant	Intron 6 of 6	1
AP3S1	ENST00000505423.1	n.73-5123G>A		intron_variant	Intron 1 of 1	2
AP3S1	ENST00000506430.2	n.*5+1378G>A		intron_variant	Intron 6 of 7	5		ENSP00000446179.1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59943 AN: 151734 Hom.: 12118 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.395 AC: 60037 AN: 151854 Hom.: 12147 Cov.: 32 AF XY: 0.400 AC XY: 29696 AN XY: 74216

African (AFR) AF: 0.456 AC: 18881 AN: 41434

American (AMR) AF: 0.480 AC: 7323 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1125 AN: 3468

East Asian (EAS) AF: 0.334 AC: 1725 AN: 5164

South Asian (SAS) AF: 0.367 AC: 1763 AN: 4804

European-Finnish (FIN) AF: 0.421 AC: 4442 AN: 10542

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23698 AN: 67872

Other (OTH) AF: 0.391 AC: 822 AN: 2102

Alfa AF: 0.395 Hom.: 1549

Bravo AF: 0.401

Asia WGS AF: 0.365 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.33
PhyloP100		1.1
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: rs3756555; hg19: chr5-115243936; COSMIC: COSV57474099; COSMIC: COSV57474099;