chr5-115894028-G-A

Position:

• chr5-115894028-G-A

Variant summary

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

The NM_001284.4(AP3S1):​c.274-1059G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 151,966 control chromosomes in the GnomAD database, including 4,184 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 0.22 (4184 hom., cov: 32)
• Consequence: AP3S1 NM_001284.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.802

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP3S1	NM_001284.4	c.274-1059G>A		intron_variant		ENST00000316788.12	NP_001275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP3S1	ENST00000316788.12	c.274-1059G>A		intron_variant		1	NM_001284.4	ENSP00000325369	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33170 AN: 151848 Hom.: 4170 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.0730

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.219 AC: 33222 AN: 151966 Hom.: 4184 Cov.: 32 AF XY: 0.214 AC XY: 15915 AN XY: 74280

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0733

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.223

Alfa AF: 0.195 Hom.: 6252

Bravo AF: 0.225

Asia WGS AF: 0.0640 AC: 226 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	0.12
DANN	Benign	0.21

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: rs6882704; hg19: chr5-115229725; COSMIC: COSV57473990; COSMIC: COSV57473990;