5-140561643-A-T

Variant names:

• chr5-140561643-A-T
• rs250430
• NM_133173.3:c.691T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133173.3(APBB3):​c.691T>A​(p.Cys231Ser) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: APBB3 NM_133173.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.74
• Publications: 40 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19889116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBB3	NM_133173.3	c.691T>A	p.Cys231Ser	missense_variant	Exon 8 of 13	ENST00000357560.9	NP_573419.2
APBB3	NM_006051.4	c.712T>A	p.Cys238Ser	missense_variant	Exon 8 of 13		NP_006042.3
APBB3	NM_133172.3	c.706T>A	p.Cys236Ser	missense_variant	Exon 7 of 12		NP_573418.2
APBB3	NM_133174.3	c.685T>A	p.Cys229Ser	missense_variant	Exon 7 of 12		NP_573420.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBB3	ENST00000357560.9	c.691T>A	p.Cys231Ser	missense_variant	Exon 8 of 13	5	NM_133173.3	ENSP00000350171.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 82

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 200537

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.021	T;.;.;T;.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	0.0037
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;T;T;T;T;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.20	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;.;.;N;.;.
PhyloP100		6.7
PrimateAI	Benign	0.32	T
PROVEAN	Benign	1.8	N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.041	D;D;D;D;D;D
Sift4G	Uncertain	0.012	D;T;T;D;D;D
Polyphen		0.0, 0.0010	.;B;.;.;B;B
Vest4		0.17
MutPred		0.60		.;.;.;.;Gain of glycosylation at C229 (P = 0.0749);Gain of glycosylation at C229 (P = 0.0749);
MVP		0.43
MPC		0.31
ClinPred		0.60	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.054
gMVP		0.63
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs250430; hg19: chr5-139941228;