Variant 12-19439767-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_153207.5(AEBP2):c.68G>C(p.Gly23Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000366 in 1,365,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

AEBP2
NM_153207.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82

Variant links:

Genes affected

AEBP2 (HGNC:24051): (AE binding protein 2) Predicted to enable transcription coregulator activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within regulation of transcription, DNA-templated. Located in nucleoplasm. Part of ESC/E(Z) complex. [provided by Alliance of Genome Resources, Apr 2022]

AEBP2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1618278).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AEBP2	NM_153207.5 link	c.68G>C	p.Gly23Ala	missense_variant	1/8	ENST00000266508.14	NP_694939.2	Q6ZN18-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AEBP2	ENST00000266508.14 link	c.68G>C	p.Gly23Ala	missense_variant	1/8	1	NM_153207.5	ENSP00000266508.9	Q6ZN18-2
AEBP2	ENST00000398864.7 link	c.68G>C	p.Gly23Ala	missense_variant	1/9	1		ENSP00000381840.3	Q6ZN18-1
AEBP2	ENST00000541908.5 link	c.-16-22743G>C		intron_variant		3		ENSP00000437983.1	G5EA50
AEBP2	ENST00000538425.5 link	c.-16-22743G>C		intron_variant		4		ENSP00000444255.1	F5GZR7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000184

AC:

AN:

108950

Hom.:

AF XY:

0.00

AC XY:

AN XY:

60734

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000280

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:

0.00000366

AC:

AN:

1365196

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

673636

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000921

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.34e-7

Gnomad4 OTH exome

AF:

0.0000175

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2024

The c.68G>C (p.G23A) alteration is located in exon 1 (coding exon 1) of the AEBP2 gene. This alteration results from a G to C substitution at nucleotide position 68, causing the glycine (G) at amino acid position 23 to be replaced by an alanine (A). 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

Benign

0.093

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.78

T;T

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.0

N;N

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.44

N;N

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.19

T;T

Polyphen

0.0030

B;.

Vest4

0.10

MutPred

0.15

Loss of catalytic residue at G23 (P = 0.0081);Loss of catalytic residue at G23 (P = 0.0081);

MVP

0.093

MPC

1.2

ClinPred

0.39

GERP RS

2.9

Varity_R

0.19

gMVP

0.42

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

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