Genetic Variant APBA3:p.Glu516Lys (chr19-3751299-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP3BP4

The NM_004886.4(APBA3):c.1546G>A(p.Glu516Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000257 in 1,539,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

APBA3
NM_004886.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.56

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, Cadd, Dann, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate [when max_spliceai, M_CAP, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.40751135).

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.1546G>A	p.Glu516Lys	missense	Exon 10 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.1546G>A	p.Glu516Lys	missense	Exon 10 of 11	ENSP00000315136.2	O96018
APBA3	ENST00000590064.1	TSL:1	n.3921G>A		non_coding_transcript_exon	Exon 3 of 4
APBA3	ENST00000591678.1	TSL:1	n.433G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000309

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000138

AC:

AN:

144524

AF XY:

0.0000774

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000808

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000112

Gnomad NFE exome

AF:

0.000266

Gnomad OTH exome

AF:

0.000234

GnomAD4 exome

AF:

0.000266

AC:

369

AN:

1387488

Hom.:

Cov.:

AF XY:

0.000257

AC XY:

176

AN XY:

684384

show subpopulations

African (AFR)

AF:

0.0000316

AC:

AN:

31632

American (AMR)

AF:

0.0000559

AC:

AN:

35760

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25094

East Asian (EAS)

AF:

0.00

AC:

AN:

35834

South Asian (SAS)

AF:

0.0000505

AC:

AN:

79166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4314

European-Non Finnish (NFE)

AF:

0.000294

AC:

317

AN:

1077934

Other (OTH)

AF:

0.000780

AC:

AN:

57690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

103

129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000171

AC:

AN:

151992

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.0000967

AC:

AN:

41358

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68000

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.000277

Hom.:

Bravo

AF:

0.000166

ExAC

AF:

0.0000371

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

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.083

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.38

MutationAssessor

Pathogenic

3.5

PhyloP100

7.6

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.37

Sift

Uncertain

0.023

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.87

MVP

0.57

MPC

0.35

ClinPred

0.96

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.55

gMVP

0.75

Mutation Taster

=27/73

disease causing

(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