rs1874147

Positions:

• chr10-74142900-C-A

Variant summary

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

The NM_012095.6(AP3M1):​c.-3-4518G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,026 control chromosomes in the GnomAD database, including 22,554 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 0.53 (22554 hom., cov: 33)
• Consequence: AP3M1 NM_012095.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309

Genes affected

AP3M1 (HGNC:569): (adaptor related protein complex 3 subunit mu 1) The protein encoded by this gene is the medium subunit of AP-3, which is an adaptor-related protein complex associated with the Golgi region as well as more peripheral intracellular structures. AP-3 facilitates the budding of vesicles from the Golgi membrane, and it may directly function in protein sorting to the endosomal/lysosomal system. AP-3 is a heterotetrameric protein complex composed of two large subunits (delta and beta3), a medium subunit (mu3), and a small subunit (sigma 3). Mutations in one of the large subunits of AP-3 have been associated with the Hermansky-Pudlak syndrome, a genetic disorder characterized by defective lysosome-related organelles. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2016]

AP3M1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP3M1	NM_012095.6	c.-3-4518G>T		intron_variant		ENST00000355264.9	NP_036227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP3M1	ENST00000355264.9	c.-3-4518G>T		intron_variant		1	NM_012095.6	ENSP00000347408.4
AP3M1	ENST00000372745.1	c.-129-3969G>T		intron_variant		1		ENSP00000361831.1
AP3M1	ENST00000487653.1	n.424-4518G>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80972 AN: 151906 Hom.: 22545 Cov.: 33

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.533 AC: 80992 AN: 152026 Hom.: 22554 Cov.: 33 AF XY: 0.530 AC XY: 39352 AN XY: 74312

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.578

Alfa AF: 0.572 Hom.: 3150

Bravo AF: 0.521

Asia WGS AF: 0.327 AC: 1141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.0
DANN	Benign	0.67

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: rs1874147; hg19: chr10-75902658;