Genetic Variant AIDA:p.Gly236Asp (chr1-222670250-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022831.4(AIDA):c.707G>A(p.Gly236Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000048 in 1,459,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

AIDA
NM_022831.4 missense, splice_region

Scores

Splicing: ADA: 0.9999

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87

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]

AIDA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIDA	NM_022831.4 link	c.707G>A	p.Gly236Asp	missense_variant, splice_region_variant	Exon 9 of 10	ENST00000340020.11	NP_073742.2	Q96BJ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIDA	ENST00000340020.11 link	c.707G>A	p.Gly236Asp	missense_variant, splice_region_variant	Exon 9 of 10	1	NM_022831.4	ENSP00000339161.6		Q96BJ3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248470

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134394

show subpopulations

Gnomad AFR exome

AF:

0.0000627

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1459844

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726224

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.707G>A (p.G236D) alteration is located in exon 9 (coding exon 9) of the AIDA gene. This alteration results from a G to A substitution at nucleotide position 707, causing the glycine (G) at amino acid position 236 to be replaced by an aspartic acid (D). 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

0.90

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;T

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.6

L;.

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.1

D;D

REVEL

Uncertain

0.35

Sift

Benign

0.18

T;D

Sift4G

Benign

0.65

T;T

Polyphen

1.0

D;.

Vest4

0.52

MutPred

0.76

Gain of solvent accessibility (P = 0.0281);.;

MVP

0.60

MPC

1.7

ClinPred

0.66

GERP RS

6.1

Varity_R

0.42

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.92

SpliceAI score (max)

0.090

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over