rs250430

chr5-140561643-A-Cchr5-140561643-A-Gchr5-140561643-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_133173.3(APBB3):c.691T>G(p.Cys231Gly) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C231R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: APBB3 NM_133173.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.74

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24221197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APBB3	NM_133173.3	c.691T>G	p.Cys231Gly	missense_variant	8/13	ENST00000357560.9
APBB3	NM_006051.4	c.712T>G	p.Cys238Gly	missense_variant	8/13
APBB3	NM_133172.3	c.706T>G	p.Cys236Gly	missense_variant	7/12
APBB3	NM_133174.3	c.685T>G	p.Cys229Gly	missense_variant	7/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APBB3	ENST00000357560.9	c.691T>G	p.Cys231Gly	missense_variant	8/13	5	NM_133173.3	A1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251432 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135886

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 82 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	23
Dann	Benign	0.95
DEOGEN2	Benign	0.024	T;.;.;T;.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	0.0037
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;T;T;T;T;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.24	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.90	N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0050	D;D;D;D;D;D
Sift4G	Uncertain	0.014	D;D;D;D;D;D
Polyphen		0.0, 0.0010	.;B;.;.;B;B
Vest4		0.17
MutPred		0.58		.;.;.;.;Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.53
MPC		0.31
ClinPred		0.43	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.70

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

Other links and lift over

dbSNP: rs250430; hg19: chr5-139941228;