9-69431371-T-C

Variant names:

• chr9-69431371-T-C
• NM_001163.4:c.2470A>G

Variant summary

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

The NM_001163.4(APBA1):​c.2470A>G​(p.Met824Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: APBA1 NM_001163.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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.2470A>G	p.Met824Val	missense_variant	Exon 13 of 13	ENST00000265381.7	NP_001154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBA1	ENST00000265381.7	c.2470A>G	p.Met824Val	missense_variant	Exon 13 of 13	1	NM_001163.4	ENSP00000265381.3
APBA1	ENST00000699288.1	c.1315A>G	p.Met439Val	missense_variant	Exon 12 of 12			ENSP00000514269.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2470A>G (p.M824V) alteration is located in exon 13 (coding exon 12) of the APBA1 gene. This alteration results from a A to G substitution at nucleotide position 2470, causing the methionine (M) at amino acid position 824 to be replaced by a valine (V). 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	0.56
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.72	D
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.38
Sift	Benign	0.030	D
Sift4G	Uncertain	0.026	D
Polyphen		0.82	P
Vest4		0.76
MutPred		0.43		Loss of phosphorylation at T829 (P = 0.0836);
MVP		0.77
MPC		0.60
ClinPred		0.94	D
GERP RS		5.2
Varity_R		0.40
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr9-72046287;