Variant rs201041158 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138368.5(AP5B1):c.1201C>T(p.Leu401Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,599,532 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 15 hom. )

Consequence

AP5B1
NM_138368.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.81

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009311676).

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP5B1	NM_138368.5 linkuse as main transcript	c.1201C>T	p.Leu401Phe	missense_variant	2/2	ENST00000532090.3	NP_612377.4	Q2VPB7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP5B1	ENST00000532090.3 linkuse as main transcript	c.1201C>T	p.Leu401Phe	missense_variant	2/2	1	NM_138368.5	ENSP00000454303.1		Q2VPB7

Frequencies

GnomAD3 genomes

AF:

0.00313

AC:

476

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00541

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00310

AC:

726

AN:

234356

Hom.:

AF XY:

0.00304

AC XY:

388

AN XY:

127682

show subpopulations

Gnomad AFR exome

AF:

0.000466

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00103

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000813

Gnomad FIN exome

AF:

0.00128

Gnomad NFE exome

AF:

0.00529

Gnomad OTH exome

AF:

0.00388

GnomAD4 exome

AF:

0.00432

AC:

6256

AN:

1447172

Hom.:

Cov.:

AF XY:

0.00418

AC XY:

3002

AN XY:

718470

show subpopulations

Gnomad4 AFR exome

AF:

0.000692

Gnomad4 AMR exome

AF:

0.00248

Gnomad4 ASJ exome

AF:

0.000918

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000997

Gnomad4 FIN exome

AF:

0.00157

Gnomad4 NFE exome

AF:

0.00517

Gnomad4 OTH exome

AF:

0.00372

GnomAD4 genome

AF:

0.00312

AC:

476

AN:

152360

Hom.:

Cov.:

AF XY:

0.00294

AC XY:

219

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000649

Gnomad4 AMR

AF:

0.00300

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00541

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00478

Hom.:

Bravo

AF:

0.00322

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.000956

AC:

ESP6500EA

AF:

0.00499

AC:

ExAC

AF:

0.00344

AC:

415

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Unit for Genetic & Epidemiological Research on Neurological Disorders, Instituto de Investigação e Inovação em Saúde

Mar 07, 2017

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0086

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.75

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.0093

MutationAssessor

Uncertain

2.9

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.32

Sift

Benign

0.21

Sift4G

Pathogenic

0.0

Vest4

0.50

MVP

0.60

MPC

0.41

GERP RS

5.0

Varity_R

0.064

gMVP

0.45

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