rs1874147

Variant names:

• chr10-74142900-C-A
• rs1874147
• NM_012095.6:c.-3-4518G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012095.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3M1	NM_012095.6	MANE Select	c.-3-4518G>T		intron	N/A	NP_036227.1	Q9Y2T2
	AP3M1	NM_001320263.2		c.-129-3969G>T		intron	N/A	NP_001307192.1	Q9Y2T2
	AP3M1	NM_001320264.2		c.-3-4518G>T		intron	N/A	NP_001307193.1	Q9Y2T2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3M1	ENST00000355264.9	TSL:1 MANE Select	c.-3-4518G>T		intron	N/A	ENSP00000347408.4	Q9Y2T2
	AP3M1	ENST00000372745.1	TSL:1	c.-129-3969G>T		intron	N/A	ENSP00000361831.1	Q9Y2T2
	AP3M1	ENST00000867215.1		c.-3-4518G>T		intron	N/A	ENSP00000537274.1

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

African (AFR) AF: 0.409 AC: 16954 AN: 41456

American (AMR) AF: 0.535 AC: 8186 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2517 AN: 3468

East Asian (EAS) AF: 0.295 AC: 1523 AN: 5160

South Asian (SAS) AF: 0.427 AC: 2061 AN: 4830

European-Finnish (FIN) AF: 0.566 AC: 5973 AN: 10550

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.617 AC: 41930 AN: 67960

Other (OTH) AF: 0.578 AC: 1221 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.0
DANN	Benign	0.67
PhyloP100		-0.31
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: rs1874147; hg19: chr10-75902658;