rs899360874

Variant names:

• chr15-82659619-C-G
• rs899360874
• NM_001278512.2:c.3247G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-82659619-C-G
• chr15-82659619-C-T

Variant summary

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

The NM_001278512.2(AP3B2):​c.3247G>C​(p.Glu1083Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,664 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1083K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AP3B2 NM_001278512.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.71
• Publications: 0 publications found

Genes affected

AP3B2 (HGNC:567): (adaptor related protein complex 3 subunit beta 2) Adaptor protein complex 3 (AP-3 complex) is a heterotrimeric protein complex involved in the formation of clathrin-coated synaptic vesicles. The protein encoded by this gene represents the beta subunit of the neuron-specific AP-3 complex and was first identified as the target antigen in human paraneoplastic neurologic disorders. The encoded subunit binds clathrin and is phosphorylated by a casein kinase-like protein, which mediates synaptic vesicle coat assembly. Defects in this gene are a cause of early-onset epileptic encephalopathy. [provided by RefSeq, Feb 2017]

CPEB1-AS1 (HGNC:27523): (CPEB1 antisense RNA 1)

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278512.2. 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
	AP3B2	NM_001278512.2	MANE Select	c.3247G>C	p.Glu1083Gln	missense	Exon 27 of 27	NP_001265441.1	Q13367-4
	AP3B2	NM_004644.5		c.3190G>C	p.Glu1064Gln	missense	Exon 26 of 26	NP_004635.2
	AP3B2	NM_001278511.2		c.3094G>C	p.Glu1032Gln	missense	Exon 25 of 25	NP_001265440.1	Q13367-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP3B2	ENST00000535359.6	TSL:1 MANE Select	c.3247G>C	p.Glu1083Gln	missense	Exon 27 of 27	ENSP00000440984.1	Q13367-4
	AP3B2	ENST00000261722.8	TSL:1	c.3208G>C	p.Glu1070Gln	missense	Exon 26 of 26	ENSP00000261722.4	A0A5F9UJV3
	AP3B2	ENST00000535348.5	TSL:1	c.3094G>C	p.Glu1032Gln	missense	Exon 25 of 25	ENSP00000438721.1	Q13367-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461664 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727122

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111862

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.80	D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	0.017	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		7.7
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.63
MutPred		0.48		Gain of MoRF binding (P = 0.0527)
MVP		0.65
MPC		0.14
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.46
gMVP		0.64

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: rs899360874; hg19: chr15-83328371;