Variant 11-65778901-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_138368.5(AP5B1):c.1592C>T(p.Pro531Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000657 in 1,611,816 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00068 ( 5 hom. )

Consequence

AP5B1
NM_138368.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011137724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP5B1	NM_138368.5 linkuse as main transcript	c.1592C>T	p.Pro531Leu	missense_variant	2/2	ENST00000532090.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP5B1	ENST00000532090.3 linkuse as main transcript	c.1592C>T	p.Pro531Leu	missense_variant	2/2	1	NM_138368.5	P1

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000656

AC:

161

AN:

245260

Hom.:

AF XY:

0.000718

AC XY:

AN XY:

133618

show subpopulations

Gnomad AFR exome

AF:

0.000331

Gnomad AMR exome

AF:

0.000613

Gnomad ASJ exome

AF:

0.00122

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00145

Gnomad FIN exome

AF:

0.0000472

Gnomad NFE exome

AF:

0.000660

Gnomad OTH exome

AF:

0.000841

GnomAD4 exome

AF:

0.000678

AC:

990

AN:

1459470

Hom.:

Cov.:

AF XY:

0.000693

AC XY:

503

AN XY:

725974

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000583

Gnomad4 ASJ exome

AF:

0.000999

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00179

Gnomad4 FIN exome

AF:

0.0000955

Gnomad4 NFE exome

AF:

0.000640

Gnomad4 OTH exome

AF:

0.000929

GnomAD4 genome

AF:

0.000453

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000445

Hom.:

Bravo

AF:

0.000359

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000482

AC:

ESP6500EA

AF:

0.000237

AC:

ExAC

AF:

0.000587

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000535

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 12, 2022

The c.1421C>T (p.P474L) 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 1421, causing the proline (P) at amino acid position 474 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.42

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.042

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.011

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.9

Sift

Uncertain

0.013

Sift4G

Uncertain

0.012

Vest4

0.083

MVP

0.45

MPC

0.10

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.042

gMVP

0.26

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