19-3751478-G-C

Variant names:

• chr19-3751478-G-C
• NM_004886.4:c.1471C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004886.4(APBA3):​c.1471C>G​(p.Pro491Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: APBA3 NM_004886.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.81

Genes affected

APBA3 (HGNC:580): (amyloid beta precursor protein binding family A member 3) The protein encoded by this gene is a member of the X11 protein family. It is an adapter protein that interacts with the Alzheimer's disease amyloid precursor protein. This gene product is believed to be involved in signal transduction processes. This gene is a candidate gene for Alzheimer's disease. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42234254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APBA3	NM_004886.4	c.1471C>G	p.Pro491Ala	missense_variant	Exon 9 of 11	ENST00000316757.4	NP_004877.1
APBA3	XM_006722950.5	c.1471C>G	p.Pro491Ala	missense_variant	Exon 9 of 10		XP_006723013.1
APBA3	XM_006722951.4	c.745C>G	p.Pro249Ala	missense_variant	Exon 7 of 8		XP_006723014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APBA3	ENST00000316757.4	c.1471C>G	p.Pro491Ala	missense_variant	Exon 9 of 11	1	NM_004886.4	ENSP00000315136.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416868 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 701858

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.15e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Benign	0.22
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.61	P
Vest4		0.47
MutPred		0.39		Gain of catalytic residue at P491 (P = 0.0634);
MVP		0.30
MPC		0.067
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.59
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-3751476;