Variant rs8102086 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004886.4(APBA3):c.1126T>G(p.Cys376Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00755 in 1,613,188 control chromosomes in the GnomAD database, including 740 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C376R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.038 ( 394 hom., cov: 34)

Exomes 𝑓: 0.0044 ( 346 hom. )

Consequence

APBA3
NM_004886.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.967

Variant links:

Genes affected

APBA3 (HGNC:580): (amyloid beta precursor protein binding family A member 3) The protein encoded by this gene is a member of the X11 protein family. It is an adapter protein that interacts with the Alzheimer's disease amyloid precursor protein. This gene product is believed to be involved in signal transduction processes. This gene is a candidate gene for Alzheimer's disease. [provided by RefSeq, Jul 2008]

APBA3 links:

APBA3 (HGNC:):

APBA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037506819).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APBA3	NM_004886.4 linkuse as main transcript	c.1126T>G	p.Cys376Gly	missense_variant	7/11	ENST00000316757.4	NP_004877.1	O96018
APBA3	XM_006722950.5 linkuse as main transcript	c.1126T>G	p.Cys376Gly	missense_variant	7/10		XP_006723013.1
APBA3	XM_006722951.4 linkuse as main transcript	c.400T>G	p.Cys134Gly	missense_variant	5/8		XP_006723014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
APBA3	ENST00000316757.4 linkuse as main transcript	c.1126T>G	p.Cys376Gly	missense_variant	7/11	1	NM_004886.4	ENSP00000315136.2	O96018
APBA3	ENST00000590064.1 linkuse as main transcript	n.3397T>G		non_coding_transcript_exon_variant	1/4	1
APBA3	ENST00000588984.5 linkuse as main transcript	n.970T>G		non_coding_transcript_exon_variant	4/8	2
APBA3	ENST00000592826.1 linkuse as main transcript	n.400T>G		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.0378

AC:

5748

AN:

152030

Hom.:

390

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0168

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000853

Gnomad OTH

AF:

0.0283

GnomAD3 exomes

AF:

0.0102

AC:

2556

AN:

249796

Hom.:

151

AF XY:

0.00756

AC XY:

1023

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.00724

Gnomad ASJ exome

AF:

0.00150

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000850

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000834

Gnomad OTH exome

AF:

0.00443

GnomAD4 exome

AF:

0.00439

AC:

6414

AN:

1461040

Hom.:

346

Cov.:

AF XY:

0.00389

AC XY:

2825

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.140

Gnomad4 AMR exome

AF:

0.00785

Gnomad4 ASJ exome

AF:

0.00241

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000916

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000522

Gnomad4 OTH exome

AF:

0.00982

GnomAD4 genome

AF:

0.0379

AC:

5768

AN:

152148

Hom.:

394

Cov.:

AF XY:

0.0354

AC XY:

2636

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.0167

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000854

Gnomad4 OTH

AF:

0.0280

Alfa

AF:

0.000283

Hom.:

32357

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.0123

AC:

1493

EpiCase

AF:

0.00115

EpiControl

AF:

0.00136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.45

DEOGEN2

Benign

0.059

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.12

MetaRNN

Benign

0.0038

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.2

PrimateAI

Benign

0.36

PROVEAN

Benign

1.5

REVEL

Benign

0.039

Sift

Benign

0.48

Sift4G

Benign

0.21

Polyphen

0.0

Vest4

0.020

MPC

0.058

ClinPred

0.0016

GERP RS

1.8

Varity_R

0.028

gMVP

0.62

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over