NM_001163.4:c.1693C>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. R565H) 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APBA1	NM_001163.4	MANE Select	c.1693C>G	p.Arg565Gly	missense	Exon 8 of 13	NP_001154.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APBA1	ENST00000265381.7	TSL:1 MANE Select	c.1693C>G	p.Arg565Gly	missense	Exon 8 of 13	ENSP00000265381.3	Q02410-1
	APBA1	ENST00000699288.1		c.538C>G	p.Arg180Gly	missense	Exon 7 of 12	ENSP00000514269.1	A0A8V8TPS8
	APBA1	ENST00000470082.2	TSL:2	c.304C>G	p.Arg102Gly	missense	Exon 3 of 3	ENSP00000486435.1	A0A0D9SFA9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.4
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
Mutation Taster		=46/54	disease causing

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

Other links and lift over

hg19: chr9-72071258;