rs3797568

chr5-115875527-A-Gchr5-115875527-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001284.4(AP3S1):c.273+5399A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,004 control chromosomes in the GnomAD database, including 11,241 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 0.38 (11241 hom., cov: 32)
• Consequence: AP3S1 NM_001284.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP3S1	NM_001284.4	c.273+5399A>G		intron_variant		ENST00000316788.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP3S1	ENST00000316788.12	c.273+5399A>G		intron_variant		1	NM_001284.4	P1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57057 AN: 151886 Hom.: 11213 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.376 AC: 57146 AN: 152004 Hom.: 11241 Cov.: 32 AF XY: 0.379 AC XY: 28140 AN XY: 74294

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.380

Alfa AF: 0.338 Hom.: 4687

Bravo AF: 0.388

Asia WGS AF: 0.328 AC: 1142 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.48

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: rs3797568; hg19: chr5-115211224; COSMIC: COSV57473859;