chr1-222703195-C-T

Variant names:

• chr1-222703195-C-T
• NM_022831.4:c.133G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52

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]

ACMG classification

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
AIDA	NM_022831.4	c.133G>A	p.Glu45Lys	missense_variant	Exon 2 of 10	ENST00000340020.11	NP_073742.2
AIDA	XM_047428100.1	c.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
AIDA	ENST00000340020.11	c.133G>A	p.Glu45Lys	missense_variant	Exon 2 of 10	1	NM_022831.4	ENSP00000339161.6

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

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;