Variant chr19-3751030-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004886.4(APBA3):c.1724T>C(p.Leu575Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000142 in 1,406,750 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

APBA3
NM_004886.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.70

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APBA3	NM_004886.4 linkuse as main transcript	c.1724T>C	p.Leu575Pro	missense_variant	11/11	ENST00000316757.4	NP_004877.1	O96018
APBA3	XM_006722950.5 linkuse as main transcript	c.1828T>C	p.Cys610Arg	missense_variant	10/10		XP_006723013.1
APBA3	XM_006722951.4 linkuse as main transcript	c.1102T>C	p.Cys368Arg	missense_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.1724T>C	p.Leu575Pro	missense_variant	11/11	1	NM_004886.4	ENSP00000315136.2	O96018
APBA3	ENST00000590064.1 linkuse as main transcript	n.4099T>C		non_coding_transcript_exon_variant	4/4	1
APBA3	ENST00000588984.5 linkuse as main transcript	n.1568T>C		non_coding_transcript_exon_variant	8/8	2
APBA3	ENST00000591678.1 linkuse as main transcript	n.*36T>C		downstream_gene_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1406750

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694608

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000548

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Sep 04, 2024

The c.1724T>C (p.L575P) alteration is located in exon 11 (coding exon 10) of the APBA3 gene. This alteration results from a T to C substitution at nucleotide position 1724, causing the leucine (L) at amino acid position 575 to be replaced by a proline (P). 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

Pathogenic

0.94

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.49

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.053

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-5.3

REVEL

Uncertain

0.35

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.35

MutPred

0.35

Gain of glycosylation at L575 (P = 0.0209);

MVP

0.34

MPC

0.38

ClinPred

1.0

GERP RS

4.6

Varity_R

0.81

gMVP

0.90

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