rs773195273

Variant names:

• chr15-82659599-G-A
• rs773195273
• NM_001278512.2:c.3267C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-82659599-G-A
• chr15-82659599-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001278512.2(AP3B2):​c.3267C>T​(p.Thr1089Thr) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T1089T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AP3B2 NM_001278512.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.73
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 15-82659599-G-A is Benign according to our data. Variant chr15-82659599-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2058655.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.73 with no splicing effect.

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.3267C>T	p.Thr1089Thr	synonymous	Exon 27 of 27	NP_001265441.1	Q13367-4
	AP3B2	NM_004644.5		c.3210C>T	p.Thr1070Thr	synonymous	Exon 26 of 26	NP_004635.2
	AP3B2	NM_001278511.2		c.3114C>T	p.Thr1038Thr	synonymous	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.3267C>T	p.Thr1089Thr	synonymous	Exon 27 of 27	ENSP00000440984.1	Q13367-4
	AP3B2	ENST00000261722.8	TSL:1	c.3228C>T	p.Thr1076Thr	synonymous	Exon 26 of 26	ENSP00000261722.4	A0A5F9UJV3
	AP3B2	ENST00000535348.5	TSL:1	c.3114C>T	p.Thr1038Thr	synonymous	Exon 25 of 25	ENSP00000438721.1	Q13367-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_noAF	Benign	-0.37
CADD	Benign	8.7
DANN	Benign	0.86
PhyloP100		2.7

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: rs773195273; hg19: chr15-83328351; COSMIC: COSV105064887; COSMIC: COSV105064887;