rs370688256

Variant names:

• chr9-69456353-C-A
• rs370688256
• NM_001163.4:c.1682G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-69456353-C-A
• chr9-69456353-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001163.4(APBA1):​c.1682G>T​(p.Arg561Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R561Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APBA1 NM_001163.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.77

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.879

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBA1	NM_001163.4	c.1682G>T	p.Arg561Leu	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.1682G>T	p.Arg561Leu	missense_variant	Exon 8 of 13	1	NM_001163.4	ENSP00000265381.3
APBA1	ENST00000699288.1	c.527G>T	p.Arg176Leu	missense_variant	Exon 7 of 12			ENSP00000514269.1
APBA1	ENST00000470082.2	c.293G>T	p.Arg98Leu	missense_variant	Exon 3 of 3	2		ENSP00000486435.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;.
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;.
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.2	M;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.2	D;.
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.0020	D;.
Polyphen		1.0	D;.
Vest4		0.82
MutPred		0.74		Loss of MoRF binding (P = 0.0268);.;
MVP		0.63
MPC		1.4
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.86
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs370688256; hg19: chr9-72071269;