5-140558653-G-C

Variant summary

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

The NM_133173.3(APBB3):ā€‹c.1393C>Gā€‹(p.Arg465Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.000016 ( 0 hom. )

Consequence

APBB3
NM_133173.3 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.03
Variant links:
Genes affected
APBB3 (HGNC:20708): (amyloid beta precursor protein binding family B member 3) The protein encoded by this gene is a member of the APBB protein family. It is found in the cytoplasm and binds to the intracellular domain of the Alzheimer's disease beta-amyloid precursor protein (APP) as well as to other APP-like proteins. It is thought that the protein encoded by this gene may modulate the internalization of APP. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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
APBB3NM_133173.3 linkuse as main transcriptc.1393C>G p.Arg465Gly missense_variant 13/13 ENST00000357560.9 NP_573419.2 O95704-1Q59EH2Q96DX9
APBB3NM_006051.4 linkuse as main transcriptc.1414C>G p.Arg472Gly missense_variant 13/13 NP_006042.3 O95704-4Q59EH2Q96DX9
APBB3NM_133172.3 linkuse as main transcriptc.1408C>G p.Arg470Gly missense_variant 12/12 NP_573418.2 O95704-3Q59EH2Q96DX9
APBB3NM_133174.3 linkuse as main transcriptc.1387C>G p.Arg463Gly missense_variant 12/12 NP_573420.2 O95704-2Q59EH2Q96DX9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
APBB3ENST00000357560.9 linkuse as main transcriptc.1393C>G p.Arg465Gly missense_variant 13/135 NM_133173.3 ENSP00000350171.4 O95704-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251034
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135778
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461812
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000189
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsJun 13, 2022The c.1393C>G (p.R465G) alteration is located in exon 13 (coding exon 13) of the APBB3 gene. This alteration results from a C to G substitution at nucleotide position 1393, causing the arginine (R) at amino acid position 465 to be replaced by a glycine (G). 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
0.087
BayesDel_addAF
Benign
-0.097
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.039
.;.;T;.
Eigen
Uncertain
0.28
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Benign
0.67
D
LIST_S2
Uncertain
0.92
D;D;D;D
M_CAP
Benign
0.022
T
MetaRNN
Uncertain
0.48
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
.;.;N;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.85
N;N;N;N
REVEL
Benign
0.14
Sift
Benign
0.098
T;T;T;T
Sift4G
Benign
0.30
T;T;T;T
Polyphen
0.99
D;.;.;D
Vest4
0.62
MutPred
0.25
Loss of helix (P = 0.0123);.;.;.;
MVP
0.48
MPC
1.0
ClinPred
0.63
D
GERP RS
5.0
Varity_R
0.096
gMVP
0.49

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.

Other links and lift over

dbSNP: rs374702672; hg19: chr5-139938238; API