Variant 11-65777906-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138368.5(AP5B1):c.2587G>A(p.Val863Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000934 in 1,552,888 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00097 ( 1 hom. )

Consequence

AP5B1
NM_138368.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.447

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026156604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP5B1	NM_138368.5 linkuse as main transcript	c.2587G>A	p.Val863Met	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.2587G>A	p.Val863Met	missense_variant	2/2	1	NM_138368.5	ENSP00000454303	P1

Frequencies

GnomAD3 genomes

AF:

0.000571

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000462

AC:

AN:

155850

Hom.:

AF XY:

0.000453

AC XY:

AN XY:

83856

show subpopulations

Gnomad AFR exome

AF:

0.000385

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000179

Gnomad SAS exome

AF:

0.0000428

Gnomad FIN exome

AF:

0.000583

Gnomad NFE exome

AF:

0.000923

Gnomad OTH exome

AF:

0.000229

GnomAD4 exome

AF:

0.000973

AC:

1363

AN:

1400516

Hom.:

Cov.:

AF XY:

0.000916

AC XY:

633

AN XY:

691196

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.0000279

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000834

Gnomad4 SAS exome

AF:

0.0000501

Gnomad4 FIN exome

AF:

0.000270

Gnomad4 NFE exome

AF:

0.00121

Gnomad4 OTH exome

AF:

0.000551

GnomAD4 genome

AF:

0.000571

AC:

AN:

152372

Hom.:

Cov.:

AF XY:

0.000550

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000829

Hom.:

Bravo

AF:

0.000620

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000257

AC:

ESP6500EA

AF:

0.000617

AC:

ExAC

AF:

0.000176

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Apr 24, 2024

The c.2416G>A (p.V806M) alteration is located in exon 1 (coding exon 1) of the AP5B1 gene. This alteration results from a G to A substitution at nucleotide position 2416, causing the valine (V) at amino acid position 806 to be replaced by a methionine (M). 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

0.22

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0091

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.026

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.33

Sift

Benign

0.16

Sift4G

Pathogenic

0.0

Vest4

0.30

MVP

0.58

MPC

0.26

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.048

gMVP

0.43

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