chr1-222703195-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022831.4(AIDA):​c.133G>A​(p.Glu45Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

AIDA
NM_022831.4 missense

Scores

5
5
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.52
Variant links:
Genes affected
AIDA (HGNC:25761): (axin interactor, dorsalization associated) Predicted to enable phosphatidylinositol binding activity. Acts upstream of or within negative regulation of JUN kinase activity. Predicted to be located in cytoplasm. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

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=0.32555598).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AIDANM_022831.4 linkc.133G>A p.Glu45Lys missense_variant Exon 2 of 10 ENST00000340020.11 NP_073742.2 Q96BJ3-1
AIDAXM_047428100.1 linkc.133G>A p.Glu45Lys missense_variant Exon 2 of 7 XP_047284056.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AIDAENST00000340020.11 linkc.133G>A p.Glu45Lys missense_variant Exon 2 of 10 1 NM_022831.4 ENSP00000339161.6 Q96BJ3-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 18, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.133G>A (p.E45K) alteration is located in exon 2 (coding exon 2) of the AIDA gene. This alteration results from a G to A substitution at nucleotide position 133, causing the glutamic acid (E) at amino acid position 45 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.92
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.038
T;.
Eigen
Uncertain
0.66
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-0.54
T
MutationAssessor
Uncertain
2.2
M;M
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-0.67
N;N
REVEL
Benign
0.16
Sift
Benign
0.25
T;T
Sift4G
Benign
0.58
T;T
Polyphen
0.95
P;.
Vest4
0.49
MutPred
0.64
Gain of ubiquitination at E45 (P = 0.0267);Gain of ubiquitination at E45 (P = 0.0267);
MVP
0.56
MPC
2.4
ClinPred
0.87
D
GERP RS
5.7
Varity_R
0.38
gMVP
0.66

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: chr1-222876537; API