dbSNP rs747345950: APLP1:p.Arg124Gly (chr19-35870974-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001024807.3(APLP1):c.370C>G(p.Arg124Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000444 in 1,575,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

APLP1
NM_001024807.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.09

Variant links:

Genes affected

APLP1 (HGNC:597): (amyloid beta precursor like protein 1) This gene encodes a member of the highly conserved amyloid precursor protein gene family. The encoded protein is a membrane-associated glycoprotein that is cleaved by secretases in a manner similar to amyloid beta A4 precursor protein cleavage. This cleavage liberates an intracellular cytoplasmic fragment that may act as a transcriptional activator. The encoded protein may also play a role in synaptic maturation during cortical development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

APLP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13601229).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APLP1	NM_001024807.3 link	c.370C>G	p.Arg124Gly	missense_variant	Exon 3 of 17	ENST00000221891.9	NP_001019978.1	P51693-2
APLP1	NM_005166.5 link	c.370C>G	p.Arg124Gly	missense_variant	Exon 3 of 17		NP_005157.1	P51693-1
APLP1	XM_017026737.3 link	c.370C>G	p.Arg124Gly	missense_variant	Exon 3 of 16		XP_016882226.1
APLP1	XM_017026738.3 link	c.370C>G	p.Arg124Gly	missense_variant	Exon 3 of 16		XP_016882227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APLP1	ENST00000221891.9 link	c.370C>G	p.Arg124Gly	missense_variant	Exon 3 of 17	1	NM_001024807.3	ENSP00000221891.4		P51693-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000215

AC:

AN:

186424

Hom.:

AF XY:

0.0000100

AC XY:

AN XY:

100002

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000115

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000414

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000351

AC:

AN:

1423504

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

704876

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000796

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000248

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000836

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Uncertain

0.098

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

T;.;.;.;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.48

LIST_S2

Uncertain

0.88

D;D;D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.14

T;T;T;T;T

MetaSVM

Uncertain

0.26

MutationAssessor

Benign

-0.42

.;N;.;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.0

N;N;.;.;.

REVEL

Benign

0.28

Sift

Uncertain

0.016

D;D;.;.;.

Sift4G

Uncertain

0.018

D;D;D;T;T

Polyphen

0.0070

B;B;B;.;.

Vest4

0.20

MutPred

0.51

.;Loss of solvent accessibility (P = 0.0329);.;.;.;

MVP

0.78

MPC

0.44

ClinPred

0.21

GERP RS

5.0

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over