Variant 11-65778436-G-A 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.2057C>T(p.Ala686Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,575,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

AP5B1
NM_138368.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.36

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=0.039883584).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP5B1	NM_138368.5 linkuse as main transcript	c.2057C>T	p.Ala686Val	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.2057C>T	p.Ala686Val	missense_variant	2/2	1	NM_138368.5	ENSP00000454303.1		Q2VPB7

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000272

AC:

AN:

184076

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

101258

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000360

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000293

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1423124

Hom.:

Cov.:

AF XY:

0.0000283

AC XY:

AN XY:

705600

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000102

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000185

Gnomad4 SAS exome

AF:

0.0000241

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000191

Gnomad4 OTH exome

AF:

0.0000506

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000586

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000336

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 02, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.0022

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.59

M_CAP

Benign

0.055

MetaRNN

Benign

0.040

MutationAssessor

Benign

0.17

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.81

Sift

Benign

0.37

Sift4G

Benign

0.99

Vest4

0.016

MVP

0.53

MPC

0.065

GERP RS

1.3

Varity_R

0.015

gMVP

0.31

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