19-35871020-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2
The NM_001024807.3(APLP1):c.416G>A(p.Arg139His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000719 in 1,530,726 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000073 ( 0 hom. )
Consequence
APLP1
NM_001024807.3 missense
NM_001024807.3 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 0.0960
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP6
Variant 19-35871020-G-A is Benign according to our data. Variant chr19-35871020-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3127854.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
APLP1 | NM_001024807.3 | c.416G>A | p.Arg139His | missense_variant | 3/17 | ENST00000221891.9 | NP_001019978.1 | |
APLP1 | NM_005166.5 | c.416G>A | p.Arg139His | missense_variant | 3/17 | NP_005157.1 | ||
APLP1 | XM_017026737.3 | c.416G>A | p.Arg139His | missense_variant | 3/16 | XP_016882226.1 | ||
APLP1 | XM_017026738.3 | c.416G>A | p.Arg139His | missense_variant | 3/16 | XP_016882227.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APLP1 | ENST00000221891.9 | c.416G>A | p.Arg139His | missense_variant | 3/17 | 1 | NM_001024807.3 | ENSP00000221891 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000725 AC: 10AN: 1378518Hom.: 0 Cov.: 31 AF XY: 0.00000737 AC XY: 5AN XY: 678378
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74358
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 03, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;T;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.;.;.
REVEL
Uncertain
Sift
Benign
T;T;.;.;.
Sift4G
Benign
T;T;T;T;T
Polyphen
B;B;B;.;.
Vest4
MutPred
0.76
.;Loss of sheet (P = 0.1158);.;.;.;
MVP
MPC
0.43
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at