Variant chr11-6402655-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001164.5(APBB1):c.1175T>C(p.Val392Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

APBB1
NM_001164.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22

Variant links:

Genes affected

APBB1 (HGNC:581): (amyloid beta precursor protein binding family B member 1) The protein encoded by this gene is a member of the Fe65 protein family. It is an adaptor protein localized in the nucleus. It interacts with the Alzheimer's disease amyloid precursor protein (APP), transcription factor CP2/LSF/LBP1 and the low-density lipoprotein receptor-related protein. APP functions as a cytosolic anchoring site that can prevent the gene product's nuclear translocation. This encoded protein could play an important role in the pathogenesis of Alzheimer's disease. It is thought to regulate transcription. Also it is observed to block cell cycle progression by downregulating thymidylate synthase expression. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Mar 2012]

APBB1 links:

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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
APBB1	NM_001164.5 linkuse as main transcript	c.1175T>C	p.Val392Ala	missense_variant	7/15	ENST00000609360.6	NP_001155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APBB1	ENST00000609360.6 linkuse as main transcript	c.1175T>C	p.Val392Ala	missense_variant	7/15	5	NM_001164.5	ENSP00000477213	A1	O00213-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

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.:

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 submitter

clinical testing

Ambry Genetics

Aug 19, 2023

The c.1175T>C (p.V392A) alteration is located in exon 7 (coding exon 6) of the APBB1 gene. This alteration results from a T to C substitution at nucleotide position 1175, causing the valine (V) at amino acid position 392 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

Uncertain

0.55

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

T;T;T;T;.;.;.;T;.;.;.;.;.;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.87

D;.;D;D;D;.;.;D;T;.;D;D;D;T

M_CAP

Benign

0.0082

MetaRNN

Uncertain

0.49

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

.;.;.;.;.;.;L;L;L;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.2

.;.;.;N;.;.;N;.;N;.;.;.;N;.

REVEL

Benign

0.23

Sift

Benign

0.079

.;.;.;T;.;.;T;.;T;.;.;.;D;.

Sift4G

Benign

0.26

T;T;T;T;T;T;T;T;T;T;T;T;T;.

Polyphen

0.30

.;.;.;.;.;.;B;.;B;.;.;.;.;.

Vest4

0.33

MutPred

0.67

.;.;.;Gain of helix (P = 0.0425);.;.;Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);.;.;.;.;.;

MVP

0.58

MPC

0.39

ClinPred

0.92

GERP RS

5.0

Varity_R

0.54

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over