rs6688

Positions:

• chr10-74121918-G-A
• chr10-74121918-G-T

Variant summary

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

The NM_012095.6(AP3M1):​c.*1892C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,100 control chromosomes in the GnomAD database, including 41,280 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 0.73 (41280 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: AP3M1 NM_012095.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP3M1	NM_012095.6	c.*1892C>T		3_prime_UTR_variant	9/9	ENST00000355264.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP3M1	ENST00000355264.9	c.*1892C>T		3_prime_UTR_variant	9/9	1	NM_012095.6	P1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110964 AN: 151982 Hom.: 41247 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.866

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.774

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.730 AC: 111050 AN: 152100 Hom.: 41280 Cov.: 32 AF XY: 0.722 AC XY: 53646 AN XY: 74328

Gnomad4 AFR AF: 0.786

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.857

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.768

Alfa AF: 0.726 Hom.: 9164

Bravo AF: 0.731

Asia WGS AF: 0.483 AC: 1683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.9
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs6688; hg19: chr10-75881676;