Variant 11-65778668-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000532090.3(AP5B1):c.1825C>T(p.Arg609Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,564,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

AP5B1
ENST00000532090.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83

Variant links:

Genes affected

AP5B1 (HGNC:25104): (adaptor related protein complex 5 subunit beta 1) Involved in endosomal transport. Located in lysosomal membrane. Part of AP-type membrane coat adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]

AP5B1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34529197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP5B1	NM_138368.5 linkuse as main transcript	c.1825C>T	p.Arg609Cys	missense_variant	2/2	ENST00000532090.3	NP_612377.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP5B1	ENST00000532090.3 linkuse as main transcript	c.1825C>T	p.Arg609Cys	missense_variant	2/2	1	NM_138368.5	ENSP00000454303	P1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000648

AC:

AN:

169732

Hom.:

AF XY:

0.0000643

AC XY:

AN XY:

93342

show subpopulations

Gnomad AFR exome

AF:

0.000106

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000611

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000948

Gnomad NFE exome

AF:

0.0000137

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000149

AC:

AN:

1411952

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

699354

show subpopulations

Gnomad4 AFR exome

AF:

0.0000616

Gnomad4 AMR exome

AF:

0.0000264

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000134

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000162

Gnomad4 NFE exome

AF:

0.00000275

Gnomad4 OTH exome

AF:

0.0000512

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000422

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 13, 2024

The c.1654C>T (p.R552C) alteration is located in exon 1 (coding exon 1) of the AP5B1 gene. This alteration results from a C to T substitution at nucleotide position 1654, causing the arginine (R) at amino acid position 552 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.77

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.35

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.96

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-6.7

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Vest4

0.48

MVP

0.57

MPC

0.41

GERP RS

4.5

Varity_R

0.33

gMVP

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over