rs5868908

Positions:

• chr5-78228244-TA-T
• chr5-78228244-TA-TAA
• chr5-78228244-TA-TAAA
• chr5-78228244-TA-TAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_003664.5(AP3B1):​c.280-6del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,558,668 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: AP3B1 NM_003664.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.10

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 5-78228244-TA-T is Benign according to our data. Variant chr5-78228244-TA-T is described in ClinVar as [Benign]. Clinvar id is 1167500.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-78228244-TA-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000528 (8/151522) while in subpopulation EAS AF= 0.000578 (3/5192). AF 95% confidence interval is 0.000157. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP3B1	NM_003664.5	c.280-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000255194.11
AP3B1	NM_001271769.2	c.133-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
AP3B1	NM_001410752.1	c.280-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP3B1	ENST00000255194.11	c.280-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003664.5	P2

Frequencies

GnomAD3 genomes AF: 0.0000528 AC: 8 AN: 151522 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000737

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000134 AC: 188 AN: 1407146 Hom.: 0 Cov.: 26 AF XY: 0.000123 AC XY: 86 AN XY: 701126

Gnomad4 AFR exome AF: 0.000188

Gnomad4 AMR exome AF: 0.000209

Gnomad4 ASJ exome AF: 0.0000399

Gnomad4 EAS exome AF: 0.000261

Gnomad4 SAS exome AF: 0.000120

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.000123

Gnomad4 OTH exome AF: 0.000137

GnomAD4 genome AF: 0.0000528 AC: 8 AN: 151522 Hom.: 0 Cov.: 0 AF XY: 0.0000676 AC XY: 5 AN XY: 73954

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000737

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000954 Hom.: 761

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hermansky-Pudlak syndrome 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs5868908; hg19: chr5-77524068;