chr5-78141213-C-A

Variant names:

• chr5-78141213-C-A
• rs779511911
• NM_003664.5:c.1580G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003664.5(AP3B1):​c.1580G>T​(p.Ser527Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AP3B1 NM_003664.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18569812).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP3B1	NM_003664.5	c.1580G>T	p.Ser527Ile	missense_variant	Exon 15 of 27	ENST00000255194.11	NP_003655.3
AP3B1	NM_001271769.2	c.1433G>T	p.Ser478Ile	missense_variant	Exon 15 of 27		NP_001258698.1
AP3B1	NM_001410752.1	c.1580G>T	p.Ser527Ile	missense_variant	Exon 15 of 23		NP_001397681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP3B1	ENST00000255194.11	c.1580G>T	p.Ser527Ile	missense_variant	Exon 15 of 27	1	NM_003664.5	ENSP00000255194.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251228 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135788

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461550 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727070

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000371 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T;.
Eigen	Benign	0.073
Eigen_PC	Benign	0.0056
FATHMM_MKL	Benign	0.12	N
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.087
Sift	Benign	0.051	T;D
Sift4G	Benign	0.081	T;T
Polyphen		0.91	P;.
Vest4		0.35
MVP		0.34
MPC		0.18
ClinPred		0.90	D
GERP RS		3.1
Varity_R		0.14
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs779511911; hg19: chr5-77437037;