9-69452297-T-C

Variant names:

• chr9-69452297-T-C
• rs1442168155
• NM_001163.4:c.1793A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001163.4(APBA1):​c.1793A>G​(p.Gln598Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar 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: 7.86
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.827

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.1793A>G	p.Gln598Arg	missense	Exon 9 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.1793A>G	p.Gln598Arg	missense	Exon 9 of 13	ENSP00000265381.3	Q02410-1
	APBA1	ENST00000699288.1		c.638A>G	p.Gln213Arg	missense	Exon 8 of 12	ENSP00000514269.1	A0A8V8TPS8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.47
Sift	Benign	0.059	T
Sift4G	Uncertain	0.029	D
Polyphen		0.99	D
Vest4		0.81
MutPred		0.60		Loss of disorder (P = 0.2977)
MVP		0.83
MPC		1.6
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.83
gMVP		0.79
Mutation Taster		=47/53	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

dbSNP: rs1442168155; hg19: chr9-72067213;