AP3B2 p.Thr1100Ser

Variant names:

• chr15-82659568-T-A
• NM_001278512.2:c.3298A>T
• AP3B2 p.Thr1100Ser

Your query was ambiguous. Multiple possible variants found:

• chr15-82659568-T-A
• chr15-82659567-G-C
• chr15-82659566-GGT-AGA
• chr15-82659566-GGT-TGA
• chr15-82659566-GGT-CGA
• chr15-82659566-GG-AC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001278512.2(AP3B2):​c.3298A>T​(p.Thr1100Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1100I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AP3B2 NM_001278512.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058875114).

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.3298A>T	p.Thr1100Ser	missense	Exon 27 of 27	NP_001265441.1	Q13367-4
	AP3B2	NM_004644.5		c.3241A>T	p.Thr1081Ser	missense	Exon 26 of 26	NP_004635.2
	AP3B2	NM_001278511.2		c.3145A>T	p.Thr1049Ser	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.3298A>T	p.Thr1100Ser	missense	Exon 27 of 27	ENSP00000440984.1	Q13367-4
	AP3B2	ENST00000261722.8	TSL:1	c.3259A>T	p.Thr1087Ser	missense	Exon 26 of 26	ENSP00000261722.4	A0A5F9UJV3
	AP3B2	ENST00000535348.5	TSL:1	c.3145A>T	p.Thr1049Ser	missense	Exon 25 of 25	ENSP00000438721.1	Q13367-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.37	N
PhyloP100		1.5
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.078
Sift	Benign	0.89	T
Sift4G	Benign	1.0	T
Varity_R		0.044
gMVP		0.093

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-83328320;