dbSNP rs370153267: APBA3:p.Leu566Pro (chr19-3751057-A-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_004886.4(APBA3):c.1697T>C(p.Leu566Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

APBA3
NM_004886.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.90

Publications

1 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:

TJP3 (HGNC:11829): (tight junction protein 3) The protein encoded by this gene is a member of the membrane-associated guanylate kinase-like (MAGUK) protein family which is characterized by members having multiple PDZ domains, a single SH3 domain, and a single guanylate kinase-like (GUK)-domain. In addition, members of the zonula occludens protein subfamily have an acidic domain, a basic arginine-rich region, and a proline-rich domain. The protein encoded by this gene plays a role in the linkage between the actin cytoskeleton and tight-junctions and also sequesters cyclin D1 at tight junctions during mitosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. This gene has a partial pseudogene on chromosome 1. [provided by RefSeq, May 2012]

TJP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.862

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APBA3	NM_004886.4	MANE Select	c.1697T>C	p.Leu566Pro	missense	Exon 11 of 11	NP_004877.1	O96018
TJP3	NM_001267560.2	MANE Select	c.*373A>G		downstream_gene	N/A	NP_001254489.1	O95049-1
TJP3	NM_001267561.2		c.*373A>G		downstream_gene	N/A	NP_001254490.1	O95049-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APBA3	ENST00000316757.4	TSL:1 MANE Select	c.1697T>C	p.Leu566Pro	missense	Exon 11 of 11	ENSP00000315136.2	O96018
APBA3	ENST00000590064.1	TSL:1	n.4072T>C		non_coding_transcript_exon	Exon 4 of 4
APBA3	ENST00000861573.1		c.1745T>C	p.Leu582Pro	missense	Exon 12 of 12	ENSP00000531632.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1413896

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698700

African (AFR)

AF:

0.00

AC:

AN:

32388

American (AMR)

AF:

0.00

AC:

AN:

37240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25324

East Asian (EAS)

AF:

0.00

AC:

AN:

37102

South Asian (SAS)

AF:

0.00

AC:

AN:

80342

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1087110

Other (OTH)

AF:

0.00

AC:

AN:

58610

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

0.99

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.86

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.8

PhyloP100

6.9

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-6.4

REVEL

Uncertain

0.57

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.97

Vest4

0.65

MutPred

0.71

Gain of disorder (P = 0.0229)

MVP

0.89

MPC

0.32

ClinPred

1.0

GERP RS

4.6

Varity_R

0.89

gMVP

0.90

Mutation Taster

=15/85

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over