Variant chr5-140560645-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_133173.3(APBB3):c.1026C>T(p.Pro342Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,613,986 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 8 hom. )

Consequence

APBB3
NM_133173.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.05

Variant links:

Genes affected

APBB3 (HGNC:20708): (amyloid beta precursor protein binding family B member 3) The protein encoded by this gene is a member of the APBB protein family. It is found in the cytoplasm and binds to the intracellular domain of the Alzheimer's disease beta-amyloid precursor protein (APP) as well as to other APP-like proteins. It is thought that the protein encoded by this gene may modulate the internalization of APP. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

APBB3 links:

APBB3 (HGNC:):

APBB3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 5-140560645-G-A is Benign according to our data. Variant chr5-140560645-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2655739.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.05 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APBB3	NM_133173.3 linkuse as main transcript	c.1026C>T	p.Pro342Pro	synonymous_variant	11/13	ENST00000357560.9	NP_573419.2	O95704-1Q59EH2Q96DX9
APBB3	NM_006051.4 linkuse as main transcript	c.1047C>T	p.Pro349Pro	synonymous_variant	11/13		NP_006042.3	O95704-4Q59EH2Q96DX9
APBB3	NM_133172.3 linkuse as main transcript	c.1041C>T	p.Pro347Pro	synonymous_variant	10/12		NP_573418.2	O95704-3Q59EH2Q96DX9
APBB3	NM_133174.3 linkuse as main transcript	c.1020C>T	p.Pro340Pro	synonymous_variant	10/12		NP_573420.2	O95704-2Q59EH2Q96DX9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APBB3	ENST00000357560.9 linkuse as main transcript	c.1026C>T	p.Pro342Pro	synonymous_variant	11/13	5	NM_133173.3	ENSP00000350171.4		O95704-1

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

386

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00432

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00234

AC:

589

AN:

251290

Hom.:

AF XY:

0.00252

AC XY:

342

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00338

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000980

Gnomad FIN exome

AF:

0.00189

Gnomad NFE exome

AF:

0.00392

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00300

AC:

4387

AN:

1461708

Hom.:

Cov.:

AF XY:

0.00309

AC XY:

2247

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00432

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00104

Gnomad4 FIN exome

AF:

0.00172

Gnomad4 NFE exome

AF:

0.00351

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.00254

AC:

387

AN:

152278

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00434

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00351

Hom.:

Bravo

AF:

0.00215

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

APBB3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.9

DANN

Benign

0.74

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