Variant 19-3751037-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004886.4(APBA3):c.1717G>A(p.Val573Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000032 in 1,560,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

APBA3
NM_004886.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.689

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25504577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APBA3	NM_004886.4 linkuse as main transcript	c.1717G>A	p.Val573Met	missense_variant	11/11	ENST00000316757.4	NP_004877.1	O96018
APBA3	XM_006722950.5 linkuse as main transcript	c.1821G>A	p.Pro607Pro	synonymous_variant	10/10		XP_006723013.1
APBA3	XM_006722951.4 linkuse as main transcript	c.1095G>A	p.Pro365Pro	synonymous_variant	8/8		XP_006723014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
APBA3	ENST00000316757.4 linkuse as main transcript	c.1717G>A	p.Val573Met	missense_variant	11/11	1	NM_004886.4	ENSP00000315136.2	O96018
APBA3	ENST00000590064.1 linkuse as main transcript	n.4092G>A		non_coding_transcript_exon_variant	4/4	1
APBA3	ENST00000588984.5 linkuse as main transcript	n.1561G>A		non_coding_transcript_exon_variant	8/8	2
APBA3	ENST00000591678.1 linkuse as main transcript	n.*29G>A		downstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000296

AC:

AN:

169140

Hom.:

AF XY:

0.0000335

AC XY:

AN XY:

89592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000426

Gnomad FIN exome

AF:

0.000189

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000215

GnomAD4 exome

AF:

0.0000305

AC:

AN:

1408484

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

695570

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000626

Gnomad4 FIN exome

AF:

0.000282

Gnomad4 NFE exome

AF:

0.0000203

Gnomad4 OTH exome

AF:

0.0000343

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000340

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 22, 2023

The c.1717G>A (p.V573M) alteration is located in exon 11 (coding exon 10) of the APBA3 gene. This alteration results from a G to A substitution at nucleotide position 1717, causing the valine (V) at amino acid position 573 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.60

M_CAP

Benign

0.013

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.6

REVEL

Benign

0.050

Sift

Benign

0.052

Sift4G

Benign

0.15

Polyphen

1.0

Vest4

0.34

MVP

0.25

MPC

0.12

ClinPred

0.15

GERP RS

0.84

Varity_R

0.043

gMVP

0.48

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