dbSNP rs757097521: APLP1:p.Thr111Lys (chr19-35870936-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001024807.3(APLP1):c.332C>A(p.Thr111Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,600,422 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

APLP1
NM_001024807.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.96

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:

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ACMG classification

Classification made for transcript

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=0.18475461).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APLP1	NM_001024807.3 link	c.332C>A	p.Thr111Lys	missense_variant	Exon 3 of 17	ENST00000221891.9	NP_001019978.1	P51693-2
APLP1	NM_005166.5 link	c.332C>A	p.Thr111Lys	missense_variant	Exon 3 of 17		NP_005157.1	P51693-1
APLP1	XM_017026737.3 link	c.332C>A	p.Thr111Lys	missense_variant	Exon 3 of 16		XP_016882226.1
APLP1	XM_017026738.3 link	c.332C>A	p.Thr111Lys	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.332C>A	p.Thr111Lys	missense_variant	Exon 3 of 17	1	NM_001024807.3	ENSP00000221891.4		P51693-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1448198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718790

show subpopulations

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:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.015

T;.;.;.;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.79

T;T;T;T;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.18

T;T;T;T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

0.46

.;N;.;.;.

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.73

N;N;.;.;.

REVEL

Benign

0.19

Sift

Benign

0.041

D;D;.;.;.

Sift4G

Benign

0.18

T;T;T;T;T

Polyphen

0.011

B;B;P;.;.

Vest4

0.22

MutPred

0.57

.;Gain of ubiquitination at T111 (P = 0.017);.;.;.;

MVP

0.55

MPC

0.46

ClinPred

0.18

GERP RS

2.6

gMVP

0.35

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