chr5-78128123-A-G

Variant names:

• chr5-78128123-A-G
• rs1305099986
• NM_003664.5:c.1875T>C

Variant summary

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

The NM_003664.5(AP3B1):​c.1875T>C​(p.Thr625Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T625T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AP3B1 NM_003664.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424
• 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: 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 (BayesDel_noAF=-0.67).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3B1	NM_003664.5	c.1875T>C	p.Thr625Thr	synonymous_variant	Exon 17 of 27	ENST00000255194.11	NP_003655.3
AP3B1	NM_001271769.2	c.1728T>C	p.Thr576Thr	synonymous_variant	Exon 17 of 27		NP_001258698.1
AP3B1	NM_001410752.1	c.1875T>C	p.Thr625Thr	synonymous_variant	Exon 17 of 23		NP_001397681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11	c.1875T>C	p.Thr625Thr	synonymous_variant	Exon 17 of 27	1	NM_003664.5	ENSP00000255194.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.2
DANN	Benign	0.69
PhyloP100		0.42

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: rs1305099986; hg19: chr5-77423947;