15-29053918-G-T

Variant names:

• chr15-29053918-G-T
• rs149792305
• NM_001353788.2:c.34G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001353788.2(APBA2):​c.34G>T​(p.Gly12Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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. G12S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APBA2 NM_001353788.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

Genes affected

APBA2 (HGNC:579): (amyloid beta precursor protein binding family A member 2) 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 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16422516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBA2	NM_001353788.2	c.34G>T	p.Gly12Cys	missense_variant	Exon 4 of 15	ENST00000683413.1	NP_001340717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBA2	ENST00000683413.1	c.34G>T	p.Gly12Cys	missense_variant	Exon 4 of 15		NM_001353788.2	ENSP00000507394.1

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	Benign	0.073
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T;.;T;T;.;T;.;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.83	.;.;.;T;T;T;T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;L;.;L;L;.;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.94	N;N;N;N;N;N;D;D;N
REVEL	Benign	0.15
Sift	Uncertain	0.0040	D;D;D;D;D;D;D;.;D
Sift4G	Uncertain	0.059	T;T;T;D;T;T;D;T;D
Polyphen		0.84	P;P;.;.;P;.;.;.;.
Vest4		0.22
MutPred		0.23		Loss of glycosylation at S11 (P = 0.0364);Loss of glycosylation at S11 (P = 0.0364);Loss of glycosylation at S11 (P = 0.0364);Loss of glycosylation at S11 (P = 0.0364);Loss of glycosylation at S11 (P = 0.0364);Loss of glycosylation at S11 (P = 0.0364);Loss of glycosylation at S11 (P = 0.0364);Loss of glycosylation at S11 (P = 0.0364);Loss of glycosylation at S11 (P = 0.0364);
MVP		0.57
MPC		0.91
ClinPred		0.54	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.16
gMVP		0.20

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: rs149792305; hg19: chr15-29346121;