chr5-140560420-T-C

Position:

• chr5-140560420-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133173.3(APBB3):​c.1117A>G​(p.Thr373Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: APBB3 NM_133173.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.23

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]

APBB3 (HGNC:):

ACMG classification

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=0.2636958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APBB3	NM_133173.3	c.1117A>G	p.Thr373Ala	missense_variant	12/13	ENST00000357560.9	NP_573419.2
APBB3	NM_006051.4	c.1138A>G	p.Thr380Ala	missense_variant	12/13		NP_006042.3
APBB3	NM_133172.3	c.1132A>G	p.Thr378Ala	missense_variant	11/12		NP_573418.2
APBB3	NM_133174.3	c.1111A>G	p.Thr371Ala	missense_variant	11/12		NP_573420.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APBB3	ENST00000357560.9	c.1117A>G	p.Thr373Ala	missense_variant	12/13	5	NM_133173.3	ENSP00000350171.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2024

The c.1117A>G (p.T373A) alteration is located in exon 12 (coding exon 12) of the APBB3 gene. This alteration results from a A to G substitution at nucleotide position 1117, causing the threonine (T) at amino acid position 373 to be replaced by an alanine (A). 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	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0057	T;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.90	T
PROVEAN	Benign	-0.41	N;N
REVEL	Benign	0.083
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.86	.;P
Vest4		0.38
MutPred		0.37		.;Gain of MoRF binding (P = 3e-04);
MVP		0.63
ClinPred		0.94	D
GERP RS		5.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-139940005;