rs796065047
Positions:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM2PP5BP4BS2
The NM_012096.3(APPL1):c.280G>A(p.Asp94Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,456,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
APPL1
NM_012096.3 missense
NM_012096.3 missense
Scores
3
6
10
Clinical Significance
Conservation
PhyloP100: 7.71
Genes affected
APPL1 (HGNC:24035): (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) The protein encoded by this gene has been shown to be involved in the regulation of cell proliferation, and in the crosstalk between the adiponectin signalling and insulin signalling pathways. The encoded protein binds many other proteins, including RAB5A, DCC, AKT2, PIK3CA, adiponectin receptors, and proteins of the NuRD/MeCP1 complex. This protein is found associated with endosomal membranes, but can be released by EGF and translocated to the nucleus. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-57238111-G-A is Pathogenic according to our data. Variant chr3-57238111-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 208075.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2576988). . Strength limited to SUPPORTING due to the PP5.
BS2
?
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APPL1 | NM_012096.3 | c.280G>A | p.Asp94Asn | missense_variant | 4/22 | ENST00000288266.8 | |
APPL1 | XM_011533583.4 | c.229G>A | p.Asp77Asn | missense_variant | 5/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APPL1 | ENST00000288266.8 | c.280G>A | p.Asp94Asn | missense_variant | 4/22 | 1 | NM_012096.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248002Hom.: 0 AF XY: 0.00000747 AC XY: 1AN XY: 133880
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000343 AC: 5AN: 1456032Hom.: 0 Cov.: 29 AF XY: 0.00000552 AC XY: 4AN XY: 724114
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
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33
Bravo
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Maturity-onset diabetes of the young type 14 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 02, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Uncertain
D;D
Polyphen
P;B
Vest4
MutPred
Loss of ubiquitination at K91 (P = 0.0566);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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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