NM_003664.5:c.3278A>G

Variant names:

• chr5-78002909-T-C
• NM_003664.5:c.3278A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003664.5(AP3B1):​c.3278A>G​(p.Gln1093Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AP3B1 NM_003664.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.86
• Publications: 0 publications found

Genes affected

AP3B1 (HGNC:566): (adaptor related protein complex 3 subunit beta 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. The encoded protein is part of the heterotetrameric AP-3 protein complex which interacts with the scaffolding protein clathrin. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

AP3B1 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3B1	NM_003664.5	c.3278A>G	p.Gln1093Arg	missense_variant	Exon 27 of 27	ENST00000255194.11	NP_003655.3
AP3B1	NM_001271769.2	c.3131A>G	p.Gln1044Arg	missense_variant	Exon 27 of 27		NP_001258698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11	c.3278A>G	p.Gln1093Arg	missense_variant	Exon 27 of 27	1	NM_003664.5	ENSP00000255194.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jun 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3278A>G (p.Q1093R) alteration is located in exon 27 (coding exon 27) of the AP3B1 gene. This alteration results from a A to G substitution at nucleotide position 3278, causing the glutamine (Q) at amino acid position 1093 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.3	M;.
PhyloP100		4.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.018	D;D
Sift4G	Benign	0.11	T;T
Polyphen		0.99	D;.
Vest4		0.64
MutPred		0.28		Gain of MoRF binding (P = 0.0021);.;
MVP		0.79
MPC		0.053
ClinPred		0.89	D
GERP RS		5.9
Varity_R		0.33
gMVP		0.32
Mutation Taster		=57/43	polymorphism

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

hg19: chr5-77298733; COSMIC: COSV99672720; COSMIC: COSV99672720;