Genetic Variant APBA3:p.Val478Ile (chr19-3751517-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004886.4(APBA3):c.1432G>A(p.Val478Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,588,818 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 4 hom. )

Consequence

APBA3
NM_004886.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

Publications

2 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019021183).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004886.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APBA3	NM_004886.4	MANE Select	c.1432G>A	p.Val478Ile	missense	Exon 9 of 11	NP_004877.1	O96018

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APBA3	ENST00000316757.4	TSL:1 MANE Select	c.1432G>A	p.Val478Ile	missense	Exon 9 of 11	ENSP00000315136.2	O96018
APBA3	ENST00000590064.1	TSL:1	n.3703G>A		non_coding_transcript_exon	Exon 3 of 4
APBA3	ENST00000591678.1	TSL:1	n.215G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000225

AC:

AN:

209018

AF XY:

0.000211

show subpopulations

Gnomad AFR exome

AF:

0.0000785

Gnomad AMR exome

AF:

0.0000654

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00204

Gnomad NFE exome

AF:

0.000108

Gnomad OTH exome

AF:

0.000192

GnomAD4 exome

AF:

0.000139

AC:

199

AN:

1436506

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

108

AN XY:

713078

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32800

American (AMR)

AF:

0.00

AC:

AN:

41470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25660

East Asian (EAS)

AF:

0.00

AC:

AN:

38496

South Asian (SAS)

AF:

0.0000843

AC:

AN:

83008

European-Finnish (FIN)

AF:

0.00156

AC:

AN:

48714

Middle Eastern (MID)

AF:

0.000952

AC:

AN:

4202

European-Non Finnish (NFE)

AF:

0.0000934

AC:

103

AN:

1102818

Other (OTH)

AF:

0.000152

AC:

AN:

59338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000118

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41572

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.0000642

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.000141

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0092

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

3.1

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.87

REVEL

Benign

0.032

Sift

Benign

0.15

Sift4G

Benign

0.085

Polyphen

0.0080

Vest4

0.22

MVP

0.21

MPC

0.056

ClinPred

0.036

GERP RS

2.5

Varity_R

0.024

gMVP

0.097

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over