9-69456342-G-C

Variant names:

• chr9-69456342-G-C
• NM_001163.4:c.1693C>G

Variant summary

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

The NM_001163.4(APBA1):​c.1693C>G​(p.Arg565Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R565C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APBA1 NM_001163.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.38

Genes affected

APBA1 (HGNC:578): (amyloid beta precursor protein binding family A member 1) The protein encoded by this gene is a member of the X11 protein family. It is a neuronal adapter protein that interacts with the Alzheimer's disease amyloid precursor protein (APP). It stabilizes APP and inhibits production of proteolytic APP fragments including the A beta peptide that is deposited in the brains of Alzheimer's disease patients. This gene product is believed to be involved in signal transduction processes. It is also regarded as a putative vesicular trafficking protein in the brain that can form a complex with the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion. [provided by RefSeq, Jul 2008]

ACMG classification

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 rank	MANE	Protein	UniProt
APBA1	NM_001163.4	c.1693C>G	p.Arg565Gly	missense_variant	Exon 8 of 13	ENST00000265381.7	NP_001154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBA1	ENST00000265381.7	c.1693C>G	p.Arg565Gly	missense_variant	Exon 8 of 13	1	NM_001163.4	ENSP00000265381.3
APBA1	ENST00000699288.1	c.538C>G	p.Arg180Gly	missense_variant	Exon 7 of 12			ENSP00000514269.1
APBA1	ENST00000470082.2	c.304C>G	p.Arg102Gly	missense_variant	Exon 3 of 3	2		ENSP00000486435.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1693C>G (p.R565G) alteration is located in exon 8 (coding exon 7) of the APBA1 gene. This alteration results from a C to G substitution at nucleotide position 1693, causing the arginine (R) at amino acid position 565 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	0.24
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D;.
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.7	D;.
REVEL	Uncertain	0.30
Sift	Uncertain	0.026	D;.
Sift4G	Benign	0.13	T;.
Polyphen		1.0	D;.
Vest4		0.81
MutPred		0.62		Loss of MoRF binding (P = 0.0198);.;
MVP		0.72
MPC		0.79
ClinPred		0.97	D
GERP RS		6.1
Varity_R		0.50
gMVP		0.45

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: chr9-72071258;