NM_001261826.3:c.3040G>T

Variant names:

• chr19-2110842-C-A
• rs4806830
• NM_001261826.3:c.3040G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001261826.3(AP3D1):​c.3040G>T​(p.Val1014Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AP3D1 NM_001261826.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.90
• Publications: 1 publications found

Genes affected

AP3D1 (HGNC:568): (adaptor related protein complex 3 subunit delta 1) The protein encoded by this gene is a subunit of the AP3 adaptor-like complex, which is not clathrin-associated, but is associated with the golgi region, as well as more peripheral structures. The AP-3 complex facilitates the budding of vesicles from the golgi membrane, and may be directly involved in trafficking to lysosomes. This subunit is implicated in intracellular biogenesis and trafficking of pigment granules, and possibly platelet dense granules and neurotransmitter vesicles. Defects in this gene are a cause of a new type of Hermansky-Pudlak syndrome. [provided by RefSeq, Feb 2017]

AP3D1 Gene-Disease associations (from GenCC):

• Hermansky-Pudlak syndrome 10

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4084663).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001261826.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3D1	NM_001261826.3	MANE Select	c.3040G>T	p.Val1014Leu	missense	Exon 27 of 32	NP_001248755.1
	AP3D1	NM_001374799.1		c.3004G>T	p.Val1002Leu	missense	Exon 27 of 32	NP_001361728.1
	AP3D1	NM_003938.8		c.2854G>T	p.Val952Leu	missense	Exon 25 of 30	NP_003929.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3D1	ENST00000643116.3	MANE Select	c.3040G>T	p.Val1014Leu	missense	Exon 27 of 32	ENSP00000495274.2
	AP3D1	ENST00000345016.9	TSL:1	c.2854G>T	p.Val952Leu	missense	Exon 25 of 30	ENSP00000344055.4
	AP3D1	ENST00000591650.1	TSL:1	n.277G>T		non_coding_transcript_exon	Exon 2 of 7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.68
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.9
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.073
Sift	Benign	0.47	T
Sift4G	Benign	0.41	T
Polyphen		0.0010	B
Vest4		0.17
MutPred		0.67		Loss of catalytic residue at V952 (P = 0.0607)
MVP		0.18
MPC		0.082
ClinPred		0.28	T
GERP RS		2.6
PromoterAI		0.15	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
Varity_R		0.045
gMVP		0.16
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs4806830; hg19: chr19-2110841;